Abstract
AMP-activated protein kinase (AMPK) is a cellular energy gauge and a major regulator of cellular energy homeostasis. Once activated, AMPK stimulates nutrient uptake and the ATP-producing catabolic pathways, while it suppresses the ATP-consuming anabolic pathways, thus helping to maintain the cellular energy balance under energy-deprived conditions. As much as ~ 20–25% of the whole-body ATP consumption occurs due to a reaction catalysed by Na+,K+-ATPase (NKA). Being the single most important sink of energy, NKA might seem to be an essential target of the AMPK-mediated energy saving measures, yet NKA is vital for maintenance of transmembrane Na+ and K+ gradients, water homeostasis, cellular excitability, and the Na+-coupled transport of nutrients and ions. Consistent with the model that AMPK regulates ATP consumption by NKA, activation of AMPK in the lung alveolar cells stimulates endocytosis of NKA, thus suppressing the transepithelial ion transport and the absorption of the alveolar fluid. In skeletal muscles, contractions activate NKA, which opposes a rundown of transmembrane ion gradients, as well as AMPK, which plays an important role in adaptations to exercise. Inhibition of NKA in contracting skeletal muscle accentuates perturbations in ion concentrations and accelerates development of fatigue. However, different models suggest that AMPK does not inhibit or even stimulates NKA in skeletal muscle, which appears to contradict the idea that AMPK maintains the cellular energy balance by always suppressing ATP-consuming processes. In this short review, we examine the role of AMPK in regulation of NKA in skeletal muscle and discuss the apparent paradox of AMPK-stimulated ATP consumption.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ackermann U, Geering K (1990) Mutual dependence of Na, K-ATPase alpha- and beta-subunits for correct posttranslational processing and intracellular transport. FEBS Lett 269:105–108. https://doi.org/10.1016/0014-5793(90)81130-G
Al-Khalili L, Yu M, Chibalin AV (2003) Na+, K+-ATPase trafficking in skeletal muscle: insulin stimulates translocation of both alpha 1- and alpha 2-subunit isoforms. FEBS Lett 536:198–202. https://doi.org/10.1016/S0014579303000474
Al-Khalili L, Kotova O, Tsuchida H, Ehren I, Feraille E, Krook A, Chibalin AV (2004) ERK1/2 mediates insulin stimulation of Na(+), K(+)-ATPase by phosphorylation of the alpha-subunit in human skeletal muscle cells. J Biol Chem 279:25211–25218. https://doi.org/10.1074/jbc.M402152200
Allen DG, Eisner DA, Smith GL, Wray S (1985) The effects of an extract of the foxglove (Digitalis-Purpurea) on tension and intracellular calcium-concentration in ferret papillary-muscle. J Physiol-London 365:P55–P55
Alves DS, Farr GA, Seo-Mayer P, Caplan MJ (2010) AS160 associates with the Na+, K+-ATPase and mediates the adenosine monophosphate-stimulated protein kinase-dependent regulation of sodium pump surface expression. Mol Biol Cell 21:4400–4408. https://doi.org/10.1091/mbc.E10-06-0507
Andersen SL, Clausen T (1993) Calcitonin gene-related peptide stimulates active Na(+)-K+ transport in rat soleus muscle. Am J Physiol 264:C419-429
Andersson U et al (2004) AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 279:12005–12008. https://doi.org/10.1074/jbc.C300557200
Arystarkhova E, Bouley R, Liu YB, Sweadner KJ (2017) Impaired AQP2 trafficking in Fxyd1 knockout mice: a role for FXYD1 in regulated vesicular transport. PLoS ONE 12:e0188006. https://doi.org/10.1371/journal.pone.0188006
Askari A (2019a) The other functions of the sodium pump. Cell Calcium 84:102105. https://doi.org/10.1016/j.ceca.2019.102105
Askari A (2019b) The sodium pump and digitalis drugs: dogmas and fallacies. Pharmacol Res Perspect 7:e00505. https://doi.org/10.1002/prp2.505
Bain J et al (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297–315. https://doi.org/10.1042/BJ20070797
Baldwin RL, Smith NE, Taylor J, Sharp M (1980) Manipulating metabolic parameters to improve growth rate and milk secretion. J Anim Sci 51:1416–1428. https://doi.org/10.2527/jas1981.5161416x
Benziane B, Chibalin AV (2008) Frontiers: skeletal muscle sodium pump regulation: a translocation paradigm. Am J Physiol Endocrinol Metab 295:E553-558. https://doi.org/10.1152/ajpendo.90261.2008
Benziane B et al (2012) Activation of AMP-activated protein kinase stimulates Na+, K+-ATPase activity in skeletal muscle cells. J Biol Chem 287:23451–23463. https://doi.org/10.1074/jbc.M111.331926
Benziane B, Bjornholm M, Lantier L, Viollet B, Zierath JR, Chibalin AV (2009) AMP-activated protein kinase activator A-769662 is an inhibitor of the Na(+)-K(+)-ATPase. Am J Physiol Cell Physiol 297:C1554-1566. https://doi.org/10.1152/ajpcell.00010.2009
Benziane B, Widegren U, Pirkmajer S, Henriksson J, Stepto NK, Chibalin AV (2011) Effect of exercise and training on phospholemman phosphorylation in human skeletal muscle. Am J Physiol Endocrinol Metab 301:E456-466. https://doi.org/10.1152/ajpendo.00533.2010
Bergeron R, Russell RR 3rd, Young LH, Ren JM, Marcucci M, Lee A, Shulman GI (1999) Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 276:E938-944. https://doi.org/10.1152/ajpendo.1999.276.5.E938
Bergeron R, Previs SF, Cline GW, Perret P, Russell RR 3rd, Young LH, Shulman GI (2001) Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50:1076–1082. https://doi.org/10.2337/diabetes.50.5.1076
Bertorello AM, Aperia A, Walaas SI, Nairn AC, Greengard P (1991) Phosphorylation of the catalytic subunit of Na+, K(+)-ATPase inhibits the activity of the enzyme. Proc Natl Acad Sci USA 88:11359–11362
Bibert S, Roy S, Schaer D, Horisberger JD, Geering K (2008) Phosphorylation of phospholemman (FXYD1) by protein kinases A and C modulates distinct Na,K-ATPase isozymes. J Biol Chem 283:476–486. https://doi.org/10.1074/jbc.M705830200
Blanco G, Mercer RW (1998) Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function. Am J Physiol 275:F633-650
Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277:23977–23980. https://doi.org/10.1074/jbc.C200171200
Boon H et al (2012) Influence of chronic and acute spinal cord injury on skeletal muscle Na+-K+-ATPase and phospholemman expression in humans. Am J Physiol Endocrinol Metab 302:E864-871. https://doi.org/10.1152/ajpendo.00625.2011
Broberg S, Sahlin K (1989) Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 67:116–122. https://doi.org/10.1152/jappl.1989.67.1.116
Buhl ES, Jessen N, Schmitz O, Pedersen SB, Pedersen O, Holman GD, Lund S (2001) Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner. Diabetes 50:12–17. https://doi.org/10.2337/diabetes.50.1.12
Buttgereit F, Brand MD (1995) A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312(Pt 1):163–167. https://doi.org/10.1042/bj3120163
Carling D, Clarke PR, Zammit VA, Hardie DG (1989) Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 186:129–136. https://doi.org/10.1111/j.1432-1033.1989.tb15186.x
Carling D, Zammit VA, Hardie DG (1987) A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223:217–222. https://doi.org/10.1016/0014-5793(87)80292-2
Chibalin AV, Vasilets LA, Hennekes H, Pralong D, Geering K (1992) Phosphorylation of Na, K-ATPase alpha-subunits in microsomes and in homogenates of Xenopus oocytes resulting from the stimulation of protein kinase A and protein kinase C. J Biol Chem 267:22378–22384
Chibalin AV, Katz AI, Berggren PO, Bertorello AM (1997) Receptor-mediated inhibition of renal Na(+)-K(+)-ATPase is associated with endocytosis of its alpha- and beta-subunits. Am J Physiol 273:C1458-1465
Chibalin AV, Pedemonte CH, Katz AI, Feraille E, Berggren PO, Bertorello AM (1998a) Phosphorylation of the catalyic alpha-subunit constitutes a triggering signal for Na+, K+-ATPase endocytosis. J Biol Chem 273:8814–8819
Chibalin AV, Zierath JR, Katz AI, Berggren PO, Bertorello AM (1998b) Phosphatidylinositol 3-kinase-mediated endocytosis of renal Na+, K+-ATPase alpha subunit in response to dopamine. Mol Biol Cell 9:1209–1220
Chibalin AV et al (1999) Dopamine-induced endocytosis of Na+, K+-ATPase is initiated by phosphorylation of Ser-18 in the rat alpha subunit and Is responsible for the decreased activity in epithelial cells. J Biol Chem 274:1920–1927
Chibalin AV, Kovalenko MV, Ryder JW, Feraille E, Wallberg-Henriksson H, Zierath JR (2001) Insulin- and glucose-induced phosphorylation of the Na(+), K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle. Endocrinology 142:3474–3482. https://doi.org/10.1210/endo.142.8.8294
Chibalin AV, Heiny JA, Benziane B, Prokofiev AV, Vasiliev AV, Kravtsova VV, Krivoi II (2012) Chronic nicotine modifies skeletal muscle Na, K-ATPase activity through its interaction with the nicotinic acetylcholine receptor and phospholemman. PLoS ONE 7:e33719. https://doi.org/10.1371/journal.pone.0033719
Christiansen D (2019) Molecular stressors underlying exercise training-induced improvements in K(+) regulation during exercise and Na(+), K(+) -ATPase adaptation in human skeletal muscle. Acta Physiol (Oxf) 225:e13196. https://doi.org/10.1111/apha.13196
Christiansen D et al (2019) Cycling with blood flow restriction improves performance and muscle K(+) regulation and alters the effect of anti-oxidant infusion in humans. J Physiol 597:2421–2444. https://doi.org/10.1113/JP277657
Christiansen D, Murphy RM, Bangsbo J, Stathis CG, Bishop DJ (2018) Increased FXYD1 and PGC-1alpha mRNA after blood flow-restricted running is related to fibre type-specific AMPK signalling and oxidative stress in human muscle. Acta Physiol (Oxf) 223:e13045. https://doi.org/10.1111/apha.13045
Clausen T (1996) The Na+, K+ pump in skeletal muscle: quantification, regulation and functional significance. Acta Physiol Scand 156:227–235. https://doi.org/10.1046/j.1365-201X.1996.209000.x
Clausen T (2003) Na+-K+ pump regulation and skeletal muscle contractility. Physiol Rev 83:1269–1324. https://doi.org/10.1152/physrev.00011.2003
Clausen T (2010) Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam Clin Pharmacol 24:595–605. https://doi.org/10.1111/j.1472-8206.2010.00859.x
Clausen T, Flatman JA (1977) The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle. J Physiol 270:383–414
Clausen T, Hansen O (1977) Active Na-K transport and the rate of ouabain binding. The effect of insulin and other stimuli on skeletal muscle and adipocytes. J Physiol 270:415–430
Clausen T, Kohn PG (1977) The effect of insulin on the transport of sodium and potassium in rat soleus muscle. J Physiol 265:19–42
Clausen T, Flatman JA (1980) Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle. Br J Pharmacol 68:749–755
Clausen T, Everts ME, Kjeldsen K (1987) Quantification of the maximum capacity for active sodium-potassium transport in rat skeletal muscle. J Physiol 388:163–181
Clausen T, Nielsen OB (2007) Potassium, Na+, K+-pumps and fatigue in rat muscle. J Physiol 584:295–304. https://doi.org/10.1113/jphysiol.2007.136044
Clausen T, Van Hardeveld C, Everts ME (1991) Significance of cation transport in control of energy metabolism and thermogenesis. Physiol Rev 71:733–774
Cool B et al (2006) Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 3:403–416. https://doi.org/10.1016/j.cmet.2006.05.005
Cornelius F, Mahmmoud YA (2003) Functional modulation of the sodium pump: the regulatory proteins “Fixit.” News Physiol Sci 18:119–124
Covell JW, Braunwald E, Ross J Jr, Sonnenblick EH (1966) Studies on digitalis. XVI. Effects on myocardial oxygen consumption. J Clin Invest 45:1535–1542. https://doi.org/10.1172/JCI105460
Craig WS, Kyte J (1980) Stoichiometry and molecular weight of the minimum asymmetric unit of canine renal sodium and potassium ion-activated adenosine triphosphatase. J Biol Chem 255:6262–6269
Crambert G et al (2000) Transport and pharmacological properties of nine different human Na, K-ATPase isozymes. J Biol Chem 275:1976–1986
Crambert G, Fuzesi M, Garty H, Karlish S, Geering K (2002) Phospholemman (FXYD1) associates with Na, K-ATPase and regulates its transport properties. Proc Natl Acad Sci USA 99:11476–11481. https://doi.org/10.1073/pnas.182267299
Crane RK (1960) Intestinal absorption of sugars. Physiol Rev 40:789–825. https://doi.org/10.1152/physrev.1960.40.4.789
Dada L et al (2012) Alcohol worsens acute lung injury by inhibiting alveolar sodium transport through the adenosine A1 receptor. PLoS ONE 7:e30448. https://doi.org/10.1371/journal.pone.0030448
Dada LA, Chandel NS, Ridge KM, Pedemonte C, Bertorello AM, Sznajder JI (2003) Hypoxia-induced endocytosis of Na, K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-zeta. J Clin Invest 111:1057–1064. https://doi.org/10.1172/JCI16826
Davies SP, Helps NR, Cohen PT, Hardie DG (1995) 5’-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377:421–425. https://doi.org/10.1016/0014-5793(95)01368-7
Despa S et al (2005) Phospholemman-phosphorylation mediates the beta-adrenergic effects on Na/K pump function in cardiac myocytes. Circ Res 97:252–259. https://doi.org/10.1161/01.RES.0000176532.97731.e5
Dienel GA (2019) Brain glucose metabolism: integration of energetics with function. Physiol Rev 99:949–1045. https://doi.org/10.1152/physrev.00062.2017
DiFranco M, Hakimjavadi H, Lingrel JB, Heiny JA (2015) Na, K-ATPase alpha2 activity in mammalian skeletal muscle T-tubules is acutely stimulated by extracellular K. J Gen Physiol 146:281–294. https://doi.org/10.1085/jgp.201511407
Dlouha H, Teisinger J, Vyskocil F (1979) Activation of membrane Na+/K+-ATPase of mouse skeletal muscle by acetylcholine and its inhibition by alpha-bungarotoxin, curare and atropine. Pflug Arch 380:101–104
Dolinar K, Jan V, Pavlin M, Chibalin AV, Pirkmajer S (2018) Nucleosides block AICAR-stimulated activation of AMPK in skeletal muscle and cancer cells. Am J Physiol Cell Physiol. https://doi.org/10.1152/ajpcell.00311.2017
Egan B, Zierath JR (2013) Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 17:162–184. https://doi.org/10.1016/j.cmet.2012.12.012
Esmann M, Skou JC (1985) Occlusion of Na+ by the Na, K-ATPase in the presence of oligomycin. Biochem Biophys Res Commun 127:857–863. https://doi.org/10.1016/s0006-291x(85)80022-x
Evans AM et al (2005) Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells? J Biol Chem 280:41504–41511. https://doi.org/10.1074/jbc.M510040200
Evans AM, Hardie DG (2020) AMPK and the need to breathe and feed: what’s the matter with oxygen? Int J Mol Sci. https://doi.org/10.3390/ijms21103518
Everts ME, Clausen T (1994) Excitation-induced activation of the Na(+)-K+ pump in rat skeletal muscle. Am J Physiol 266:C925-934
Ewart HS, Klip A (1995) Hormonal regulation of the Na(+)-K(+)-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am J Physiol 269:C295-311
Feraille E et al (1999) Insulin-induced stimulation of Na+, K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10. Mol Biol Cell 10:2847–2859. https://doi.org/10.1091/mbc.10.9.2847
Feraille E, Doucet A (2001) Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev 81:345–418
Figtree GA et al (2009) Reversible oxidative modification: a key mechanism of Na+-K+ pump regulation. Circ Res 105:185–193. https://doi.org/10.1161/CIRCRESAHA.109.199547
Flatman JA, Clausen T (1979) Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle. Nature 281:580–581
Fotis H, Tatjanenko LV, Vasilets LA (1999) Phosphorylation of the alpha-subunits of the Na+/K+-ATPase from mammalian kidneys and xenopus oocytes by cGMP-dependent protein kinase results in stimulation of ATPase activity. Eur J Biochem 260:904–910
Gable ME, Abdallah SL, Najjar SM, Liu L, Askari A (2014) Digitalis-induced cell signaling by the sodium pump: on the relation of Src to Na(+)/K(+)-ATPase. Biochem Biophys Res Commun 446:1151–1154. https://doi.org/10.1016/j.bbrc.2014.03.071
Gaitanos GC, Williams C, Boobis LH, Brooks S (1993) Human muscle metabolism during intermittent maximal exercise. J Appl Physiol 75:712–719
Galuska D, Kotova O, Barres R, Chibalina D, Benziane B, Chibalin AV (2009) Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle: effects of high-fat diet and exercise. Am J Physiol Endocrinol Metab 297:E38-49. https://doi.org/10.1152/ajpendo.90990.2008
Geering K (2006) FXYD proteins: new regulators of Na-K-ATPase. Am J Physiol Renal Physiol 290:F241-250. https://doi.org/10.1152/ajprenal.00126.2005
Geering K (2008) Functional roles of Na, K-ATPase subunits. Curr Opin Nephrol Hypertens 17:526–532. https://doi.org/10.1097/MNH.0b013e3283036cbf
Glynn IM (1993) Annual review prize lecture. “All hands to the sodium pump.” J Physiol 462:1–30. https://doi.org/10.1113/jphysiol.1993.sp019540
Gowans GJ, Hawley SA, Ross FA, Hardie DG (2013) AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab 18:556–566. https://doi.org/10.1016/j.cmet.2013.08.019
Greenhaff PL, Nevill ME, Soderlund K, Bodin K, Boobis LH, Williams C, Hultman E (1994) The metabolic responses of human type I and II muscle fibres during maximal treadmill sprinting. J Physiol 478(Pt 1):149–155. https://doi.org/10.1113/jphysiol.1994.sp020238
Grimmer B, Kuebler WM (2017) The endothelium in hypoxic pulmonary vasoconstriction. J Appl Physiol 123:1635–1646. https://doi.org/10.1152/japplphysiol.00120.2017
Gusarova GA, Dada LA, Kelly AM, Brodie C, Witters LA, Chandel NS, Sznajder JI (2009) Alpha1-AMP-activated protein kinase regulates hypoxia-induced Na, K-ATPase endocytosis via direct phosphorylation of protein kinase C zeta. Mol Cell Biol 29:3455–3464. https://doi.org/10.1128/MCB.00054-09
Han F, Bossuyt J, Martin JL, Despa S, Bers DM (2010) Role of phospholemman phosphorylation sites in mediating kinase-dependent regulation of the Na+-K+-ATPase. Am J Physiol Cell Physiol 299:C1363-1369. https://doi.org/10.1152/ajpcell.00027.2010
Hansen O (2001) The alpha1 isoform of Na+, K+-ATPase in rat soleus and extensor digitorum longus. Acta Physiol Scand 173:335–341. https://doi.org/10.1046/j.1365-201X.2001.00910.x
Hardie DG (2015) AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol 33:1–7. https://doi.org/10.1016/j.ceb.2014.09.004
Hardie DG (2018) Keeping the home fires burning: AMP-activated protein kinase. J R Soc Interface. https://doi.org/10.1098/rsif.2017.0774
Hardie DG (2020) AMPK as a direct sensor of long-chain fatty acyl-CoA esters. Nat Metab. https://doi.org/10.1038/s42255-020-0249-y
Hardie DG, Ross FA, Hawley SA (2012a) AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol 19:1222–1236. https://doi.org/10.1016/j.chembiol.2012.08.019
Hardie DG, Ross FA, Hawley SA (2012b) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262. https://doi.org/10.1038/nrm3311
Hargreaves M, Spriet LL (2020) Skeletal muscle energy metabolism during exercise. Nat Metab. https://doi.org/10.1038/s42255-020-0251-4
Hawley SA et al (2005) Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2:9–19. https://doi.org/10.1016/j.cmet.2005.05.009
Hawley SA et al (2010) Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 11:554–565. https://doi.org/10.1016/j.cmet.2010.04.001
He S, Shelly DA, Moseley AE, James PF, James JH, Paul RJ, Lingrel JB (2001) The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles in skeletal muscle contractility. Am J Physiol Regul Integr Comp Physiol 281:R917-925
Heiny JA et al (2010) The nicotinic acetylcholine receptor and the Na, K-ATPase alpha2 isoform interact to regulate membrane electrogenesis in skeletal muscle. J Biol Chem 285:28614–28626. https://doi.org/10.1074/jbc.M110.150961
Hodgkin AL, Keynes RD (1955) Active transport of cations in giant axons from Sepia and Loligo. J Physiol 128:28–60. https://doi.org/10.1113/jphysiol.1955.sp005290
Homsher E (1987) Muscle enthalpy production and its relationship to actomyosin ATPase. Annu Rev Physiol 49:673–690. https://doi.org/10.1146/annurev.ph.49.030187.003325
Hulo S, Tiesset H, Lancel S, Edme JL, Viollet B, Sobaszek A, Neviere R (2011) AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice. Respir Res 12:64. https://doi.org/10.1186/1465-9921-12-64
Hundal HS, Marette A, Mitsumoto Y, Ramlal T, Blostein R, Klip A (1992) Insulin induces translocation of the alpha 2 and beta 1 subunits of the Na+/K(+)-ATPase from intracellular compartments to the plasma membrane in mammalian skeletal muscle. J Biol Chem 267:5040–5043
Hundal HS, Maxwell DL, Ahmed A, Darakhshan F, Mitsumoto Y, Klip A (1994) Subcellular distribution and immunocytochemical localization of Na, K-ATPase subunit isoforms in human skeletal muscle. Mol Membr Biol 11:255–262
Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA (2005) The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 280:29060–29066. https://doi.org/10.1074/jbc.M503824200
Ingwersen MS, Kristensen M, Pilegaard H, Wojtaszewski JF, Richter EA, Juel C (2011) Na, K-ATPase activity in mouse muscle is regulated by AMPK and PGC-1alpha. J Membr Biol 242:1–10. https://doi.org/10.1007/s00232-011-9365-7
Jensen TE, Rose AJ, Jorgensen SB, Brandt N, Schjerling P, Wojtaszewski JF, Richter EA (2007) Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am J Physiol Endocrinol Metab 292:E1308-1317. https://doi.org/10.1152/ajpendo.00456.2006
Jorgensen SB et al (2004) The alpha2–5’AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. Diabetes 53:3074–3081. https://doi.org/10.2337/diabetes.53.12.3074
Juel C, Grunnet L, Holse M, Kenworthy S, Sommer V, Wulff T (2001) Reversibility of exercise-induced translocation of Na+-K+ pump subunits to the plasma membrane in rat skeletal muscle. Pflug Arch 443:212–217. https://doi.org/10.1007/s004240100674
Juel C (2014) Oxidative stress (glutathionylation) and Na, K-ATPase activity in rat skeletal muscle. PLoS ONE 9:e110514. https://doi.org/10.1371/journal.pone.0110514.PONE-D-14-36259[pii]
Juel C, Nielsen JJ, Bangsbo J (2000) Exercise-induced translocation of Na(+)-K(+) pump subunits to the plasma membrane in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 278:R1107-1110
Juel C, Hostrup M, Bangsbo J (2015) The effect of exercise and beta2-adrenergic stimulation on glutathionylation and function of the Na, K-ATPase in human skeletal muscle. Physiol Rep. https://doi.org/10.14814/phy2.12515
Karatzaferi C, de Haan A, Ferguson RA, van Mechelen W, Sargeant AJ (2001) Phosphocreatine and ATP content in human single muscle fibres before and after maximum dynamic exercise. Pflug Arch 442:467–474
Kaushik VK, Young ME, Dean DJ, Kurowski TG, Saha AK, Ruderman NB (2001) Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle: effects of AICAR. Am J Physiol Endocrinol Metab 281:E335-340. https://doi.org/10.1152/ajpendo.2001.281.2.E335
Kjeldsen K, Norgaard A, Hansen O, Clausen T (1985) Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig. J Pharmacol Exp Ther 234:720–727
Kjobsted R et al (2017) Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK. Diabetes 66:598–612. https://doi.org/10.2337/db16-0530
Kjobsted R et al (2018) AMPK in skeletal muscle function and metabolism. FASEB J 32:1741–1777. https://doi.org/10.1096/fj.201700442R
Kjobsted R et al (2019) AMPK and TBC1D1 regulate muscle glucose uptake after, but not during, exercise and contraction. Diabetes 68:1427–1440. https://doi.org/10.2337/db19-0050
Koistinen HA, Galuska D, Chibalin AV, Yang J, Zierath JR, Holman GD, Wallberg-Henriksson H (2003) 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes. Diabetes 52:1066–1072. https://doi.org/10.2337/diabetes.52.5.1066
Kravtsova VV et al (2016) Distinct alpha2 Na, K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse. J Gen Physiol. https://doi.org/10.1085/jgp.201511494
Kravtsova VV, Vilchinskaya NA, Rozlomii VL, Shenkman BS, Krivoi II (2019) Low ouabain doses and AMP-activated protein kinase as factors supporting electrogenesis in skeletal muscle. Biochemistry (Mosc) 84:1085–1092. https://doi.org/10.1134/S0006297919090116
Kravtsova VV, Bouzinova EV, Chibalin AV, Matchkov VV, Krivoi II (2020) Isoform-specific Na, K-ATPase and membrane cholesterol remodeling in motor endplates in distinct mouse models of myodystrophy. Am J Physiol Cell Physiol 318:C1030–C1041. https://doi.org/10.1152/ajpcell.00453.2019
Kristensen M, Juel C (2010) Na+, K+-ATPase Na+ affinity in rat skeletal muscle fiber types. J Membr Biol 234:35–45. https://doi.org/10.1007/s00232-010-9237-6
Kristensen M, Rasmussen MK, Juel C (2008) Na(+)-K (+) pump location and translocation during muscle contraction in rat skeletal muscle. Pflug Arch 456:979–989. https://doi.org/10.1007/s00424-008-0449-x
Krivoi II, Drabkina TM, Kravtsova VV, Vasiliev AN, Eaton MJ, Skatchkov SN, Mandel F (2006) On the functional interaction between nicotinic acetylcholine receptor and Na+, K+-ATPase. Pflug Arch 452:756–765. https://doi.org/10.1007/s00424-006-0081-6
Kuriki Y, Racker E (1976) Inhibition of (Na+, K+)adenosine triphosphatase and its partial reactions by quercetin. Biochemistry 15:4951–4956. https://doi.org/10.1021/bi00668a001
Kutz LC et al (2018) Isoform-specific role of Na/K-ATPase alpha1 in skeletal muscle. Am J Physiol Endocrinol Metab 314:E620–E629. https://doi.org/10.1152/ajpendo.00275.2017
Kyte J (1971) Purification of the sodium- and potassium-dependent adenosine triphosphatase from canine renal medulla. J Biol Chem 246:4157–4165
Lamb JF, McCall D (1972) Effect of prolonged ouabain treatment of Na, K, Cl and Ca concentration and fluxes in cultured human cells. J Physiol 225:599–617. https://doi.org/10.1113/jphysiol.1972.sp009959
Lecuona E, Dada LA, Sun H, Butti ML, Zhou G, Chew TL, Sznajder JI (2006) Na, K-ATPase alpha1-subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane. FASEB J 20:2618–2620. https://doi.org/10.1096/fj.06-6503fje
Lee-Young RS, Griffee SR, Lynes SE, Bracy DP, Ayala JE, McGuinness OP, Wasserman DH (2009) Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo. J Biol Chem 284:23925–23934. https://doi.org/10.1074/jbc.M109.021048
Lemieux K, Konrad D, Klip A, Marette A (2003) The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases alpha and beta in skeletal muscle. FASEB J 17:1658–1665. https://doi.org/10.1096/fj.02-1125com
Li Z, Langhans SA (2015) Transcriptional regulators of Na, K-ATPase subunits. Front Cell Dev Biol 3:66. https://doi.org/10.3389/fcell.2015.00066
Lifshitz Y, Lindzen M, Garty H, Karlish SJ (2006) Functional interactions of phospholemman (PLM) (FXYD1) with Na+, K+-ATPase. Purification of alpha1/beta1/PLM complexes expressed in Pichia pastoris. J Biol Chem 281:15790–15799
Lin SC, Hardie DG (2017) AMPK: sensing glucose as well as cellular energy status. Cell Metab. https://doi.org/10.1016/j.cmet.2017.10.009
Liu CC et al (2012) Susceptibility of beta1 Na+-K+ pump subunit to glutathionylation and oxidative inhibition depends on conformational state of pump. J Biol Chem 287:12353–12364. https://doi.org/10.1074/jbc.M112.340893
Liu Y et al (2020) TLR9 and beclin 1 crosstalk regulates muscle AMPK activation in exercise. Nature 578:605–609. https://doi.org/10.1038/s41586-020-1992-7
Lubarski I, Pihakaski-Maunsbach K, Karlish SJ, Maunsbach AB, Garty H (2005) Interaction with the Na, K-ATPase and tissue distribution of FXYD5 (related to ion channel). J Biol Chem 280:37717–37724. https://doi.org/10.1074/jbc.M506397200
Lubarski I, Karlish SJ, Garty H (2007) Structural and functional interactions between FXYD5 and the Na+-K+-ATPase. Am J Physiol Renal Physiol 293:F1818-1826. https://doi.org/10.1152/ajprenal.00367.2007
Lubarski I, Asher C, Garty H (2011) FXYD5 (dysadherin) regulates the paracellular permeability in cultured kidney collecting duct cells. Am J Physiol Renal Physiol 301:F1270-1280. https://doi.org/10.1152/ajprenal.00142.2011
Lucke JC et al (1994) Effects of cardiac glycosides on myocardial function and energetics in conscious dogs. Am J Physiol 267:H2042-2049. https://doi.org/10.1152/ajpheart.1994.267.5.H2042
Luly P, Baldini P, Cocco C, Incerpi S, Tria E (1977) Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro. Eur J Pharmacol 46:153–164. https://doi.org/10.1016/0014-2999(77)90251-5
Manoharan P, Radzyukevich TL, Hakim Javadi H, Stiner C, Landero-Figurero J, Lingrel JB, Heiny JA (2015) Phospholemman is not required for the acute stimulation of Na, K-ATPase alpha2 activity during skeletal muscle fatigue. Am J Physiol Cell Physiol. https://doi.org/10.1152/ajpcell.00205.2015
Marette A, Krischer J, Lavoie L, Ackerley C, Carpentier JL, Klip A (1993) Insulin increases the Na(+)-K(+)-ATPase alpha 2-subunit in the surface of rat skeletal muscle: morphological evidence. Am J Physiol 265:C1716-1722
McBride A, Ghilagaber S, Nikolaev A, Hardie DG (2009) The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor. Cell Metab 9:23–34. https://doi.org/10.1016/j.cmet.2008.11.008
McConell GK (2020) It’s well and truly time to stop stating that AMPK regulates glucose uptake and fat oxidation during exercise. Am J Physiol Endocrinol Metab 318:E564–E567. https://doi.org/10.1152/ajpendo.00511.2019
McDonough AA, Youn JH (2017) Potassium homeostasis: the knowns, the unknowns, and the health benefits. Physiology (Bethesda) 32:100–111. https://doi.org/10.1152/physiol.00022.2016
McDonough AA, Geering K, Farley RA (1990) The sodium pump needs its beta subunit. FASEB J 4:1598–1605
Merrill GF, Kurth EJ, Hardie DG, Winder WW (1997) AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 273:E1107-1112. https://doi.org/10.1152/ajpendo.1997.273.6.E1107
Meyerson LR, McMurtrey KD, Davis VE (1978) Isoquinoline alkaloids. Inhibitory actions on cation-dependent ATP-phosphohydrolases. Neurochem Res 3:239–257. https://doi.org/10.1007/BF00964063
Michiels C (2004) Physiological and pathological responses to hypoxia. Am J Pathol 164:1875–1882. https://doi.org/10.1016/S0002-9440(10)63747-9
Minokoshi Y et al (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428:569–574. https://doi.org/10.1038/nature02440
Mishra NK et al (2015) Molecular mechanisms and kinetic effects of FXYD1 and phosphomimetic mutants on purified human Na, K-ATPase. J Biol Chem 290:28746–28759. https://doi.org/10.1074/jbc.M115.687913
Moral-Sanz J et al (2018) The LKB1-AMPK-alpha1 signaling pathway triggers hypoxic pulmonary vasoconstriction downstream of mitochondria. Sci Signal. https://doi.org/10.1126/scisignal.aau0296
Morth JP et al (2007) Crystal structure of the sodium-potassium pump. Nature 450:1043–1049. https://doi.org/10.1038/nature06419
Mukhopadhyay R, Venkatadri R, Katsnelson J, Arav-Boger R (2018) Digitoxin suppresses human cytomegalovirus replication via Na(+), K(+)/ATPase alpha1 subunit-dependent AMP-activated protein kinase and autophagy activation. J Virol. https://doi.org/10.1128/JVI.01861-17
Nielsen OB, Clausen T (1996) The significance of active Na+, K+ transport in the maintenance of contractility in rat skeletal muscle. Acta Physiol Scand 157:199–209. https://doi.org/10.1046/j.1365-201X.1996.d01-748.x
Nielsen OB, Clausen T (1997) Regulation of Na(+)-K+ pump activity in contracting rat muscle. J Physiol 503(3):571–581
Orlov SN, Taurin S, Tremblay J, Hamet P (2001) Inhibition of Na+, K+ pump affects nucleic acid synthesis and smooth muscle cell proliferation via elevation of the [Na+]i/[K+]i ratio: possible implication in vascular remodelling. J Hypertens 19:1559–1565. https://doi.org/10.1097/00004872-200109000-00007
Orlowski J, Lingrel JB (1988) Tissue-specific and developmental regulation of rat Na, K-ATPase catalytic alpha isoform and beta subunit mRNAs. J Biol Chem 263:10436–10442
Owen MR, Doran E, Halestrap AP (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348(3):607–614
Palmer CJ, Scott BT, Jones LR (1991) Purification and complete sequence determination of the major plasma membrane substrate for cAMP-dependent protein kinase and protein kinase C in myocardium. J Biol Chem 266:11126–11130
Pataky MW et al (2019) Fiber type-specific effects of acute exercise on insulin-stimulated AS160 phosphorylation in insulin-resistant rat skeletal muscle. Am J Physiol Endocrinol Metab 317:E984–E998. https://doi.org/10.1152/ajpendo.00304.2019
Perry BD et al (2013) The effects of osteoarthritis and age on skeletal muscle strength, Na+-K+-ATPase content, gene and isoform expression. J Appl Physiol 115:1443–1449. https://doi.org/10.1152/japplphysiol.00789.2013
Pestov NB et al (2007) Evolution of Na, K-ATPase beta m-subunit into a coregulator of transcription in placental mammals. Proc Natl Acad Sci USA 104:11215–11220. https://doi.org/10.1073/pnas.0704809104
Pestov NB, Zhao H, Basrur V, Modyanov NN (2011) Isolation and characterization of BetaM protein encoded by ATP1B4–a unique member of the Na, K-ATPase beta-subunit gene family. Biochem Biophys Res Commun 412:543–548. https://doi.org/10.1016/j.bbrc.2011.07.112
Petrushanko IY et al (2012) S-glutathionylation of the Na, K-ATPase catalytic alpha subunit is a determinant of the enzyme redox sensitivity. J Biol Chem 287:32195–32205. https://doi.org/10.1074/jbc.M112.391094
Pinkosky SL et al (2020) Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK beta1 isoforms. Nat Metab. https://doi.org/10.1038/s42255-020-0245-2
Pirkmajer S, Chibalin AV (2016) Na, K-ATPase regulation in skeletal muscle. Am J Physiol Endocrinol Metab 311:E1–E31. https://doi.org/10.1152/ajpendo.00539.2015
Pirkmajer S, Chibalin AV (2019) Hormonal regulation of Na(+)-K(+)-ATPase from the evolutionary perspective. Curr Top Membr 83:315–351. https://doi.org/10.1016/bs.ctm.2019.01.009
Pirkmajer S et al (2015) Methotrexate promotes glucose uptake and lipid oxidation in skeletal muscle via AMPK activation. Diabetes 64:360–369. https://doi.org/10.2337/db14-0508
Pirkmajer S et al (2017) Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport. J Physiol. https://doi.org/10.1113/JP274254
Post RL, Jolly PC (1957) The linkage of sodium, potassium, and ammonium active transport across the human erythrocyte membrane. Biochim Biophys Acta 25:118–128
Radzyukevich TL et al (2004) The Na(+)-K(+)-ATPase alpha2-subunit isoform modulates contractility in the perinatal mouse diaphragm. Am J Physiol Cell Physiol 287:C1300-1310. https://doi.org/10.1152/ajpcell.00231.2004
Radzyukevich TL, Neumann JC, Rindler TN, Oshiro N, Goldhamer DJ, Lingrel JB, Heiny JA (2013) Tissue-specific role of the Na, K-ATPase alpha2 isozyme in skeletal muscle. J Biol Chem 288:1226–1237. https://doi.org/10.1074/jbc.M112.424663
Rasmussen MK, Kristensen M, Juel C (2008) Exercise-induced regulation of phospholemman (FXYD1) in rat skeletal muscle: implications for Na+/K+-ATPase activity. Acta Physiol (Oxf) 194:67–79. https://doi.org/10.1111/j.1748-1716.2008.01857.x
Reis J et al (2005) Expression of phospholemman and its association with Na+-K+-ATPase in skeletal muscle: effects of aging and exercise training. J Appl Physiol 99:1508–1515
Robinson JD, Robinson LJ, Martin NJ (1984) Effects of oligomycin and quercetin on the hydrolytic activities of the (Na+ + K+)-dependent ATPase. Biochim Biophys Acta 772:295–306. https://doi.org/10.1016/0005-2736(84)90146-9
Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758
Ross FA, MacKintosh C, Hardie DG (2016) AMP-activated protein kinase: a cellular energy sensor that comes in 12 flavours. FEBS J 283:2987–3001. https://doi.org/10.1111/febs.13698
Rossier BC, Baker ME, Studer RA (2015) Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited. Physiol Rev 95:297–340. https://doi.org/10.1152/physrev.00011.2014
Schatzmann HJ (1953) Cardiac glycosides as inhibitors of active potassium and sodium transport by erythrocyte membrane. Helv Physiol Pharmacol Acta 11:346–354
Schatzmann HJ, Witt PN (1954) Action of k-strophanthin on potassium leakage from frog sartorius muscle. J Pharmacol Exp Ther 112:501–508
Schneider H et al (2015) AMPK dilates resistance arteries via activation of SERCA and BKCa channels in smooth muscle. Hypertension 66:108–116. https://doi.org/10.1161/HYPERTENSIONAHA.115.05514
Scott JW et al (2008) Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes. Chem Biol 15:1220–1230. https://doi.org/10.1016/j.chembiol.2008.10.005
Sejersted OM, Sjogaard G (2000) Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol Rev 80:1411–1481
Sen AK, Post RL (1964) Stoichiometry and localization of adenosine triphosphate-dependent sodium and potassium transport in the erythrocyte. J Biol Chem 239:345–352
Seo-Mayer PW, Thulin G, Zhang L, Alves DS, Ardito T, Kashgarian M, Caplan MJ (2011) Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia. Am J Physiol Renal Physiol 301:F1346-1357. https://doi.org/10.1152/ajprenal.00420.2010
Shiyan AA et al (2019) Elevation of intracellular Na(+) contributes to expression of early response genes triggered by endothelial cell shrinkage. Cell Physiol Biochem 53:638–647. https://doi.org/10.33594/000000162
Sidorenko S, Klimanova E, Milovanova K, Lopina OD, Kapilevich LV, Chibalin AV, Orlov SN (2018) Transcriptomic changes in C2C12 myotubes triggered by electrical stimulation: Role of Ca(2+)i-mediated and Ca(2+)i-independent signaling and elevated [Na(+)]i/[K(+)]i ratio. Cell Calcium 76:72–86. https://doi.org/10.1016/j.ceca.2018.09.007
Skou JC (1957) The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta 23:394–401
Spriet LL, Soderlund K, Bergstrom M, Hultman E (1987) Anaerobic energy release in skeletal muscle during electrical stimulation in men. J Appl Physiol 62:611–615. https://doi.org/10.1152/jappl.1987.62.2.611
Stremming J, Jansson T, Powell TL, Rozance PJ, Brown LD (2020) Reduced Na(+) K(+) -ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged ex vivo amino acid transporter activity. J Physiol 598:1625–1639. https://doi.org/10.1113/JP278933
Sweadner KJ, Rael E (2000) The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. Genomics 68:41–56. https://doi.org/10.1006/geno.2000.6274
Sweadner KJ, McGrail KM, Khaw BA (1992) Discoordinate regulation of isoforms of Na, K-ATPase and myosin heavy chain in the hypothyroid postnatal rat heart and skeletal muscle. J Biol Chem 267:769–773
Tan CD et al (2012) AMP-activated protein kinase (AMPK)-dependent and -independent pathways regulate hypoxic inhibition of transepithelial Na+ transport across human airway epithelial cells. Br J Pharmacol 167:368–382. https://doi.org/10.1111/j.1476-5381.2012.01993.x
Thomassen M, Christensen PM, Gunnarsson TP, Nybo L, Bangsbo J (2010) Effect of 2-wk intensified training and inactivity on muscle Na+-K+ pump expression, phospholemman (FXYD1) phosphorylation, and performance in soccer players. J Appl Physiol 108:898–905. https://doi.org/10.1152/japplphysiol.01015.2009
Thomassen M et al (2011) Protein kinase Calpha activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 301:R1808-1814. https://doi.org/10.1152/ajpregu.00066.2011
Thomassen M, Gunnarsson TP, Christensen PM, Pavlovic D, Shattock MJ, Bangsbo J (2016) Intensive training and reduced volume increases muscle FXYD1 expression and phosphorylation at rest and during exercise in athletes. Am J Physiol Regul Integr Comp Physiol 310:R659-669. https://doi.org/10.1152/ajpregu.00081.2015
Thomassen M, Murphy RM, Bangsbo J (2013) Fibre type-specific change in FXYD1 phosphorylation during acute intense exercise in humans. J Physiol 591:1523–1533. https://doi.org/10.1113/jphysiol.2012.247312
Treebak JT, Birk JB, Hansen BF, Olsen GS, Wojtaszewski JF (2009) A-769662 activates AMPK beta1-containing complexes but induces glucose uptake through a PI3-kinase-dependent pathway in mouse skeletal muscle. Am J Physiol Cell Physiol 297:C1041-1052. https://doi.org/10.1152/ajpcell.00051.2009
Vadasz I et al (2008) AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na, K-ATPase endocytosis. J Clin Invest 118:752–762. https://doi.org/10.1172/JCI29723
Walas H, Juel C (2012) Purinergic activation of rat skeletal muscle membranes increases Vmax and Na+ affinity of the Na, K-ATPase and phosphorylates phospholemman and alpha1 subunits. Pflug Arch 463:319–326. https://doi.org/10.1007/s00424-011-1050-2
Walaas SI, Czernik AJ, Olstad OK, Sletten K, Walaas O (1994) Protein kinase C and cyclic AMP-dependent protein kinase phosphorylate phospholemman, an insulin and adrenaline-regulated membrane phosphoprotein, at specific sites in the carboxy terminal domain. Biochem J 304(2):635–640
Wang YB et al (2014) Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na, K-ATPase in collecting duct principal cells. J Am Soc Nephrol 25:250–259. https://doi.org/10.1681/ASN.2013040429
Wang H, Arias EB, Oki K, Pataky MW, Almallouhi JA, Cartee GD (2019) Fiber type-selective exercise effects on AS160 phosphorylation. Am J Physiol Endocrinol Metab. https://doi.org/10.1152/ajpendo.00528.2018
Weekes J, Hawley SA, Corton J, Shugar D, Hardie DG (1994) Activation of rat liver AMP-activated protein kinase by kinase kinase in a purified, reconstituted system. Effects of AMP and AMP analogues. Eur J Biochem 219:751–757. https://doi.org/10.1111/j.1432-1033.1994.tb18554.x
Winder WW, Hardie DG (1996) Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 270:E299-304. https://doi.org/10.1152/ajpendo.1996.270.2.E299
Winder WW et al (1997) Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase. A J Appl Physiol 82:219–225. https://doi.org/10.1152/jappl.1997.82.1.219
Witt PN, Schatzmann HJ (1954) Effect of strophanthin on potassium liberation in resting and working sartorius muscle in frog. Helv Physiol Pharmacol Acta 12:C44-46
Wojtaszewski JF, Nielsen P, Hansen BF, Richter EA, Kiens B (2000) Isoform-specific and exercise intensity-dependent activation of 5’-AMP-activated protein kinase in human skeletal muscle. J Physiol 528(1):221–226
Wojtaszewski JF, Birk JB, Frosig C, Holten M, Pilegaard H, Dela F (2005) 5’AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol 564:563–573. https://doi.org/10.1113/jphysiol.2005.082669
Woods A et al (2005) Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2:21–33. https://doi.org/10.1016/j.cmet.2005.06.005
Woollhead AM, Scott JW, Hardie DG, Baines DL (2005) Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells. J Physiol 566:781–792. https://doi.org/10.1113/jphysiol.2005.088674
Woollhead AM et al (2007) Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells. Br J Pharmacol 151:1204–1215. https://doi.org/10.1038/sj.bjp.0707343
Wright EM, Loo DD, Hirayama BA (2011) Biology of human sodium glucose transporters. Physiol Rev 91:733–794. https://doi.org/10.1152/physrev.00055.2009
Wyckelsma VL, Perry BD, Bangsbo J, McKenna MJ (2019) Inactivity and exercise training differentially regulate abundance of Na(+)-K(+)-ATPase in human skeletal muscle. J Appl Physiol 127:905–920. https://doi.org/10.1152/japplphysiol.01076.2018
Xiao B et al (2011) Structure of mammalian AMPK and its regulation by ADP. Nature 472:230–233. https://doi.org/10.1038/nature09932
Xiao B et al (2013) Structural basis of AMPK regulation by small molecule activators. Nat Commun 4:3017. https://doi.org/10.1038/ncomms4017
Xiao J et al (2019) AMPK alleviates high uric acid-induced Na(+)-K(+)-ATPase signaling impairment and cell injury in renal tubules. Exp Mol Med 51:1–14. https://doi.org/10.1038/s12276-019-0254-y
Yeh LA, Ling L, English L, Cantley L (1983) Phosphorylation of the (Na, K)-ATPase by a plasma membrane-bound protein kinase in friend erythroleukemia cells. J Biol Chem 258:6567–6574
Yuan Q et al (2014) Advanced glycation end-products impair Na(+)/K(+)-ATPase activity in diabetic cardiomyopathy: role of the adenosine monophosphate-activated protein kinase/sirtuin 1 pathway. Clin Exp Pharmacol Physiol 41:127–133. https://doi.org/10.1111/1440-1681.12194
Zhang XQ et al (2003) Phospholemman modulates Na+/Ca2+ exchange in adult rat cardiac myocytes. Am J Physiol Heart Circ Physiol 284:H225-233. https://doi.org/10.1152/ajpheart.00698.2002
Zhang XQ et al (2015) Regulation of L-type calcium channel by phospholemman in cardiac myocytes. J Mol Cell Cardiol. https://doi.org/10.1016/j.yjmcc.2015.04.017
Zhang CS et al (2017) Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature 548:112–116. https://doi.org/10.1038/nature23275
Zhao S, Snow RJ, Stathis CG, Febbraio MA, Carey MF (2000) Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans. J Appl Physiol 88:1513–1519. https://doi.org/10.1152/jappl.2000.88.5.1513
Zheng D et al (2008) AMPK activation with AICAR provokes an acute fall in plasma [K+]. Am J Physiol Cell Physiol 294:C126-135. https://doi.org/10.1152/ajpcell.00464.2007
Zheng J, Ramirez VD (2000) Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals. Br J Pharmacol 130:1115–1123. https://doi.org/10.1038/sj.bjp.0703397
Zhou G et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174. https://doi.org/10.1172/JCI13505
Zong Y et al (2019) Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress. Cell Res 29:460–473. https://doi.org/10.1038/s41422-019-0163-6
Funding
S.P. and M.P. are supported by funding from the Slovenian Research Agency (Grants #P3-0043, #J7-8276, BI-HR/20-21-041, and the young researcher Grant to M.P.). A.V.C. is supported by the Swedish Research Council, the Novo Nordisk Research Foundation, the Strategic Research Programme in Diabetes at Karolinska Institutet, the Russian Scientific Foundation (RNF #19-15-00118). S.P. and A.V.C. are principal investigators of the bilateral cooperation project between Republic of Slovenia and the Russian Federation funded by the Slovenian Research Agency (BI-RU/19-20-039).
Author information
Authors and Affiliations
Contributions
S.P. and A.V.C. conceptualized the review paper. S.P. prepared the first draft of the paper. S.P. and M.P. prepared the first draft of the tables. All authors contributed to literature search and to writing of the subsequent versions of the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
There are no relevant conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pirkmajer, S., Petrič, M. & Chibalin, A.V. The role of AMPK in regulation of Na+,K+-ATPase in skeletal muscle: does the gauge always plug the sink?. J Muscle Res Cell Motil 42, 77–97 (2021). https://doi.org/10.1007/s10974-020-09594-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10974-020-09594-3