Roles of Na+, Ca2+, and K+ channels in the generation of repetitive firing and rhythmic bursting in adrenal chromaffin cells

  • Christopher J. Lingle
  • Pedro L. Martinez-Espinosa
  • Laura Guarina
  • Emilio CarboneEmail author
Invited Review


Adrenal chromaffin cells (CCs) are the main source of circulating catecholamines (CAs) that regulate the body response to stress. Release of CAs is controlled neurogenically by the activity of preganglionic sympathetic neurons through trains of action potentials (APs). APs in CCs are generated by robust depolarization following the activation of nicotinic and muscarinic receptors that are highly expressed in CCs. Bovine, rat, mouse, and human CCs also express a composite array of Na+, K+, and Ca2+ channels that regulate the resting potential, shape the APs, and set the frequency of AP trains. AP trains of increasing frequency induce enhanced release of CAs. If the primary role of CCs is simply to relay preganglionic nerve commands to CA secretion, why should they express such a diverse set of ion channels? An answer to this comes from recent observations that, like in neurons, CCs undergo complex firing patterns of APs suggesting the existence of an intrinsic CC excitability (non-neurogenically controlled). Recent work has shown that CCs undergo occasional or persistent burst firing elicited by altered physiological conditions or deletion of pore-regulating auxiliary subunits. In this review, we aim to give a rationale to the role of the many ion channel types regulating CC excitability. We will first describe their functional properties and then analyze how they contribute to pacemaking, AP shape, and burst waveforms. We will also furnish clear indications on missing ion conductances that may be involved in pacemaking and highlight the contribution of the crucial channels involved in burst firing.


Sodium channels Potassium and calcium channels Action potential Burst firing Chromaffin cell excitability Catecholamine release 


  1. 1.
    Albillos A, Artalejo AR, Lopez MG, Gandia L, Garcia AG, Carbone E (1994) Calcium channel subtypes in cat chromaffin cells. J Physiol 477:197–213Google Scholar
  2. 2.
    Albillos A, Carbone E, Gandia L, Garcia AG, Pollo A (1996) Opioid inhibition of Ca2+ channel subtypes in bovine chromaffin cells: selectivity of action and voltage dependence. Eur J Neurosci 8:1561–1570Google Scholar
  3. 3.
    Albillos A, Gandia L, Michelena P, Gilabert JA, del Valle M, Carbone E, Garcia AG (1996) The mechanism of calcium channel facilitation in bovine chromaffin cells. J Physiol 494:687–695Google Scholar
  4. 4.
    Albillos A, Neher E, Moser T (2000) R-type Ca2+ channels are coupled to the rapid component of secretion in mouse adrenal slice chromaffin cells. J Neurosci 20:8323–8330Google Scholar
  5. 5.
    Albinana E, Segura-Chama P, Baraibar AM, Hernandez-Cruz A, Hernandez-Guijo JM (2015) Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices. J Neurochem 133:511–521Google Scholar
  6. 6.
    Alvarez YD, Belingheri AV, Perez Bay AE, Javis SE, Tedford HW, Zamponi G, Marengo FD (2013) The immediately releasable pool of mouse chromaffin cell vesicles is coupled to P/Q-type calcium channels via the synaptic protein interaction site. PLoS One 8:e54846Google Scholar
  7. 7.
    Alvarez YD, Ibanez LI, Uchitel OD, Marengo FD (2008) P/Q Ca2+ channels are functionally coupled to exocytosis of the immediately releasable pool in mouse chromaffin cells. Cell Calcium 43:155–164Google Scholar
  8. 8.
    Artalejo AR, Garcia AG, Neher E (1993) Small-conductance Ca2+-activated K+ channels in bovine chromaffin cells. Pflügers Arch Eur J Physiol 423:97–103Google Scholar
  9. 9.
    Artalejo CR, Adams ME, Fox AP (1994) Three types of Ca2+ channel trigger secretion with different efficacies in chromaffin cells. Nature 367:72–76Google Scholar
  10. 10.
    Artalejo CR, Dahmer MK, Perlman RL, Fox AP (1991) Two types of Ca2+ currents are found in bovine chromaffin cells: facilitation is due to the recruitment of one type. J Physiol 432:681–707Google Scholar
  11. 11.
    Artalejo CR, Garcia AG, Aunis D (1987) Chromaffin cell calcium channel kinetics measured isotopically through fast calcium, strontium, and barium fluxes. J Biol Chem 262:915–926Google Scholar
  12. 12.
    Artalejo CR, Mogul DJ, Perlman RL, Fox AP (1991) Three types of bovine chromaffin cell Ca2+ channels: facilitation increases the opening probability of a 27 pS channel. J Physiol 444:213–240Google Scholar
  13. 13.
    Artalejo CR, Perlman RL, Fox AP (1992) Omega-conotoxin GVIA blocks a Ca2+ current in bovine chromaffin cells that is not of the “classic” N type. Neuron 8:85–95Google Scholar
  14. 14.
    Barbara JG, Poncer JC, McKinney RA, Takeda K (1998) An adrenal slice preparation for the study of chromaffin cells and their cholinergic innervation. J Neurosci Methods 80:181–189Google Scholar
  15. 15.
    Bean BP, Nowycky MC, Tsien RW (1984) β-adrenergic modulation of calcium channels in frog ventricular heart cells. Nature 307:371–375Google Scholar
  16. 16.
    Biales B, Dichter M, Tischler A (1976) Electrical excitability of cultured adrenal chromaffin cells. J Physiol 262:743–753Google Scholar
  17. 17.
    Bond CT, Maylie J, Adelman JP (2005) SK channels in excitability, pacemaking and synaptic integration. Curr Opin Neurobiol 15:305–311Google Scholar
  18. 18.
    Bournaud R, Hidalgo J, Yu H, Jaimovich E, Shimahara T (2001) Low threshold T-type calcium current in rat embryonic chromaffin cells. J Physiol 537:35–44Google Scholar
  19. 19.
    Brandt BL, Hagiwara S, Kidokoro Y, Miyazaki S (1976) Action potentials in the rat chromaffin cell and effects of acetylcholine. J Physiol 263:417–439Google Scholar
  20. 20.
    Brown DA (2013) The other (muscarinic) acetylcholine receptors in sympathetic ganglia: actions and mechanisms. Neurophysiology 45:60–66Google Scholar
  21. 21.
    Carabelli V, Carra I, Carbone E (1998) Localized secretion of ATP and opioids revealed through single Ca2+ channel modulation in bovine chromaffin cells. Neuron 20:1255–1268Google Scholar
  22. 22.
    Carabelli V, Giancippoli A, Baldelli P, Carbone E, Artalejo AR (2003) Distinct potentiation of L-type currents and secretion by cAMP in rat chromaffin cells. Biophys J 85:1326–1337Google Scholar
  23. 23.
    Carabelli V, Hernandez-Guijo JM, Baldelli P, Carbone E (2001) Direct autocrine inhibition and cAMP-dependent potentiation of single L-type Ca2+ channels in bovine chromaffin cells. J Physiol 532:73–90Google Scholar
  24. 24.
    Carabelli V, Marcantoni A, Comunanza V, Carbone E (2007) Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+-dependence. Eur Biophys J  36:753–762Google Scholar
  25. 25.
    Carabelli V, Marcantoni A, Comunanza V, de Luca A, Diaz J, Borges R, Carbone E (2007) Chronic hypoxia up-regulates α1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. J Physiol 584:149–165Google Scholar
  26. 26.
    Carbone E, Calorio C, Vandael DH (2014) T-type channel-mediated neurotransmitter release. Pflügers Arch Eur J Physiol 466:677–687Google Scholar
  27. 27.
    Carbone E, Carabelli V (2009) O2 sensing in chromaffin cells: new duties for T-type channels. J Physiol 587:1859–1860Google Scholar
  28. 28.
    Cesetti T, Hernandez-Guijo JM, Baldelli P, Carabelli V, Carbone E (2003) Opposite action of β1- and β2-adrenergic receptors on Cav1 L-channel current in rat adrenal chromaffin cells. J Neurosci 23:73–83Google Scholar
  29. 29.
    Chan SA, Hill J, Smith C (2012) Reduced calcium current density in female versus male mouse adrenal chromaffin cells in situ. Cell Calcium 52:313–320Google Scholar
  30. 30.
    Chan SA, Polo-Parada L, Smith C (2005) Action potential stimulation reveals an increased role for P/Q-calcium channel-dependent exocytosis in mouse adrenal tissue slices. Arch Biochem Biophys 435:65–73Google Scholar
  31. 31.
    Chatterjee O, Taylor LA, Ahmed S, Nagaraj S, Hall JJ, Finckbeiner SM, Chan PS, Suda N, King JT, Zeeman ML, McCobb DP (2009) Social stress alters expression of large conductance calcium-activated potassium channel subunits in mouse adrenal medulla and pituitary glands. J Neuroendocrinol 21:167–176Google Scholar
  32. 32.
    Comunanza V, Marcantoni A, Vandael DH, Mahapatra S, Gavello D, Carabelli V, Carbone E (2010) Cav1.3 as pacemaker channels in adrenal chromaffin cells: specific role on exo- and endocytosis? Channels 4:440–446Google Scholar
  33. 33.
    Coupland RE (1965) Electronic microscopic observations on the structure of the rat adrenal medulla. I. The ultrastructure and organization of chromaffin cells in normal adrenal medulla. J Anat 99:231–254Google Scholar
  34. 34.
    Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, Waxman SG (2001) Nav1.3 sodium channels: rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons. J Neurosci 21:5952–5961Google Scholar
  35. 35.
    Currie KP, Fox AP (1996) ATP serves as a negative feedback inhibitor of voltage-gated Ca2+ channel currents in cultured bovine adrenal chromaffin cells. Neuron 16:1027–1036Google Scholar
  36. 36.
    Currie KP, Fox AP (2002) Differential facilitation of N- and P/Q-type calcium channels during trains of action potential-like waveforms. J Physiol 539:419–431Google Scholar
  37. 37.
    Currie KP, Fox AP (2000) Voltage-dependent, pertussis toxin insensitive inhibition of calcium currents by histamine in bovine adrenal chromaffin cells. J Neurophysiol 83:1435–1442Google Scholar
  38. 38.
    de Diego AM, Gandia L, Garcia AG (2008) A physiological view of the central and peripheral mechanisms that regulate the release of catecholamines at the adrenal medulla. Acta Physiol 192:287–301Google Scholar
  39. 39.
    Delmas P, Brown DA (2005) Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nat Rev Neurosci 6:850–862Google Scholar
  40. 40.
    Ding JP, Li ZW, Lingle CJ (1998) Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits. Biophys J 74:268–289Google Scholar
  41. 41.
    Dorval AD (2006) The rhythmic consequences of ion channel stochasticity. Neuroscientist 12:442–448Google Scholar
  42. 42.
    Duan K, Yu X, Zhang C, Zhou Z (2003) Control of secretion by temporal patterns of action potentials in adrenal chromaffin cells. J Neurosci 23:11235–11243Google Scholar
  43. 43.
    Engisch KL, Nowycky MC (1996) Calcium dependence of large dense-cored vesicle exocytosis evoked by calcium influx in bovine adrenal chromaffin cells. J Neurosci 16:1359–1369Google Scholar
  44. 44.
    Faber ES (2009) Functions and modulation of neuronal SK channels. Cell Biochem Biophys 55:127–139Google Scholar
  45. 45.
    Faber ES, Sah P (2007) Functions of SK channels in central neurons. Clin Exp Pharmacol Physiol 34:1077–1083Google Scholar
  46. 46.
    Fakler B, Adelman JP (2008) Control of K-Ca channels by calcium nano/microdomains. Neuron 59:873–881Google Scholar
  47. 47.
    Fenwick EM, Marty A, Neher E (1982) A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol 331:577–597Google Scholar
  48. 48.
    Fenwick EM, Marty A, Neher E (1982) Sodium and calcium channels in bovine chromaffin cells. J Physiol 331:599–635Google Scholar
  49. 49.
    Gandia L, Garcia AG, Morad M (1993) ATP modulation of calcium channels in chromaffin cells. J Physiol 470:55–72Google Scholar
  50. 50.
    Gandia L, Mayorgas I, Michelena P, Cuchillo I, de Pascual R, Abad F, Novalbos JM, Larranaga E, Garcia AG (1998) Human adrenal chromaffin cell calcium channels: drastic current facilitation in cell clusters, but not in isolated cells. Pflügers Arch Eur J Physiol 436:696–704Google Scholar
  51. 51.
    Garcia AG, Garcia-De-Diego AM, Gandia L, Borges R, Garcia-Sancho J (2006) Calcium signaling and exocytosis in adrenal chromaffin cells. Physiol Rev 86:1093–1131Google Scholar
  52. 52.
    Gavello D, Rojo-Ruiz J, Marcantoni A, Franchino C, Carbone E, Carabelli V (2012) Leptin Counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study. Plos One 7:e41530Google Scholar
  53. 53.
    Gavello D, Vandael D, Gosso S, Carbone E, Carabelli V (2015) Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-driven BK channel up-regulation in mouse chromaffin cells. J Physiol 593:4835–4853Google Scholar
  54. 54.
    Giancippoli A, Novara M, de Luca A, Baldelli P, Marcantoni A, Carbone E, Carabelli V (2006) Low-threshold exocytosis induced by cAMP-recruited Cav3.2 (α1H) channels in rat chromaffin cells. Biophys J 90:1830–1841Google Scholar
  55. 55.
    Goldfarb M (2005) Fibroblast growth factor homologous factors: evolution, structure, and function. Cytokine Growth Factor Rev 16:215–220Google Scholar
  56. 56.
    Guarina L, Vandael DH, Carabelli V, Carbone E (2017) Low pHo boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. J Physiol 595:2587–2609Google Scholar
  57. 57.
    Guerineau NC, Desarmenien MG, Carabelli V, Carbone E (2012) Functional chromaffin cell plasticity in response to stress: focus on nicotinic, gap junction, and voltage-gated Ca2+ channels. J Mol Neurosci 48:368–386Google Scholar
  58. 58.
    Gullo F, Ales E, Rosati B, Lecchi M, Masi A, Guasti L, Cano-Abad MF, Arcangeli A, Lopez MG, Wanke E (2002) ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2-related sudden death? FASEB J 17:330–332Google Scholar
  59. 59.
    Guo X, Przywara DA, Wakade TD, Wakade AR (1996) Exocytosis coupled to mobilization of intracellular calcium by muscarine and caffeine in rat chromaffin cells. J Neurochem 67:155–162Google Scholar
  60. 60.
    Harada K, Matsuoka H, Miyata H, Matsui M, Inoue M (2015) Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion. Br J Pharmacol 172:1348–1359Google Scholar
  61. 61.
    Hernandez-Guijo JM, Carabelli V, Gandia L, Garcia AG, Carbone E (1999) Voltage-independent autocrine modulation of L-type channels mediated by ATP, opioids and catecholamines in rat chromaffin cells. Eur J Neurosci 11:3574–3584Google Scholar
  62. 62.
    Hernandez-Guijo JM, Gandia L, Lara B, Garcia AG (1998) Autocrine/paracrine modulation of calcium channels in bovine chromaffin cells. Pflügers Arch Eur J Physiol 437:104–113Google Scholar
  63. 63.
    Hernandez A, Segura-Chama P, Albinana E, Hernandez-Cruz A, Hernandez-Guijo JM (2010) Down-modulation of Ca2+ channels by endogenously released ATP and opioids: from the isolated chromaffin cell to the slice of adrenal medullae. Cell Mol Neurobiol 30:1209–1216Google Scholar
  64. 64.
    Herrington J, Solaro CR, Neely A, Lingle CJ (1995) The suppression of Ca2+- and voltage-dependent outward K+ current during mAChR activation in rat adrenal chromaffin cells. J Physiol 485:297–318Google Scholar
  65. 65.
    Herzog RI, Cummins TR, Ghassemi F, Dib-Hajj SD, Waxman SG (2003) Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J Physiol 551:741–750Google Scholar
  66. 66.
    Hill J, Chan SA, Kuri B, Smith C (2011) Pituitary adenylate cyclase-activating peptide (PACAP) recruits low voltage-activated T-type calcium influx under acute sympathetic stimulation in mouse adrenal chromaffin cells. J Biol Chem 286:42459–42469Google Scholar
  67. 67.
    Ho C, Zhao J, Malinowski S, Chahine M, O’Leary ME (2012) Differential expression of sodium channel β subunits in dorsal root ganglion sensory neurons. J Biol Chem 287:15044–15053Google Scholar
  68. 68.
    Hoshi T, Rothlein J, Smith SJ (1984) Facilitation of Ca2+-channel currents in bovine adrenal chromaffin cells. Proc Natl Acad Sci U S A 81:5871–5875Google Scholar
  69. 69.
    Inoue M, Harada K, Matsuoka H, Sata T, Warashina A (2008) Inhibition of TASK1-like channels by muscarinic receptor stimulation in rat adrenal medullary cells. J Neurochem 106:1804–1814Google Scholar
  70. 70.
    Inoue M, Kuriyama H (1990) Muscarine induces two distinct current responses in adrenal chromaffin cells of the guinea-pig. Jpn J Physiol 40:679–691Google Scholar
  71. 71.
    Inoue M, Kuriyama H (1991) Muscarinic receptor is coupled with a cation channel through a GTP-binding protein in guinea-pig chromaffin cells. J Physiol 436:511–529Google Scholar
  72. 72.
    Kajiwara R, Sand O, Kidokoro Y, Barish ME, Iijima T (1997) Functional organization of chromaffin cells and cholinergic synaptic transmission in rat adrenal medulla. Jpn J Physiol 47:449–464Google Scholar
  73. 73.
    Kim SJ, Lim W, Kim J (1995) Contribution of L- and N-type calcium currents to exocytosis in rat adrenal medullary chromaffin cells. Brain Res 675:289–296Google Scholar
  74. 74.
    Klingauf J, Neher E (1997) Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in neuroendocrine cells. Biophys J 72:674–690Google Scholar
  75. 75.
    Klugbauer N, Lacinova L, Flockerzi V, Hofmann F (1995) Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells. EMBO J 14:1084–1090Google Scholar
  76. 76.
    Levitsky KL, Lopez-Barneo J (2009) Developmental change of T-type Ca2+ channel expression and its role in rat chromaffin cell responsiveness to acute hypoxia. J Physiol 587:1917–1929Google Scholar
  77. 77.
    Lingle CJ, Solaro CR, Prakriya M, Ding JP (1996) Calcium-activated potassium channels in adrenal chromaffin cells. Ion Channels 4:261–301Google Scholar
  78. 78.
    Liu C, Dib-Hajj SD, Waxman SG (2001) Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN). J Biol Chem 276:18925–18933Google Scholar
  79. 79.
    Lopez MG, Albillos A, de la Fuente MT, Borges R, Gandia L, Carbone E, Garcia AG, Artalejo AR (1994) Localized L-type calcium channels control exocytosis in cat chromaffin cells. Pflügers Arch Eur J Physiol 427:348–354Google Scholar
  80. 80.
    Lopez MG, Villarroya M, Lara B, Martinez Sierra R, Albillos A, Garcia AG, Gandia L (1994) Q- and L-type Ca2+ channels dominate the control of secretion in bovine chromaffin cells. FEBS Lett 349:331–337Google Scholar
  81. 81.
    Lou XL, Yu X, Chen XK, Duan KL, He LM, Qu AL, Xu T, Zhou Z (2003) Na+ channel inactivation: a comparative study between pancreatic islet beta-cells and adrenal chromaffin cells in rat. J Physiol 548:191–202Google Scholar
  82. 82.
    Lovell PV, James DG, McCobb DP (2000) Bovine versus rat adrenal chromaffin cells: big differences in BK potassium channel properties. J Neurophysiol 83:3277–3286Google Scholar
  83. 83.
    Lovell PV, King JT, McCobb DP (2004) Acute modulation of adrenal chromaffin cell BK channel gating and cell excitability by glucocorticoids. J Neurophysiol 91:561–570Google Scholar
  84. 84.
    Lovell PV, McCobb DP (2001) Pituitary control of BK potassium channel function and intrinsic firing properties of adrenal chromaffin cells. J Neurosci 21:3429–3442Google Scholar
  85. 85.
    Lukyanetz EA, Neher E (1999) Different types of calcium channels and secretion from bovine chromaffin cells. Eur J Neurosci 11:2865–2873Google Scholar
  86. 86.
    Mahapatra S, Calorio C, Vandael DHF, Marcantoni A, Carabelli V, Carbone E (2012) Calcium channel types contributing to chromaffin cell excitability, exocytosis and endocytosis. Cell Calcium 51:321–330Google Scholar
  87. 87.
    Mahapatra S, Marcantoni A, Vandael DH, Striessnig J, Carbone E (2011) Are Cav1.3 pacemaker channels in chromaffin cells? Possible bias from resting cell conditions and DHP blockers usage. Channels 5:219–224Google Scholar
  88. 88.
    Mahapatra S, Marcantoni A, Zuccotti A, Carabelli V, Carbone E (2012) Equal sensitivity of Cav1.2 and Cav1.3 channels to the opposing modulations of PKA and PKG in mouse chromaffin cells. J Physiol 590:5053–5073Google Scholar
  89. 89.
    Maljevic S, Wuttke TV, Lerche H (2008) Nervous system Kv7 disorders: breakdown of a subthreshold brake. J Physiol 586:1791–1801Google Scholar
  90. 90.
    Marcantoni A, Baldelli P, Hernandez-Guijo JM, Comunanza V, Carabelli V, Carbone E (2007) L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion. Cell Calcium 42:397–408Google Scholar
  91. 91.
    Marcantoni A, Carabelli V, Comunanza V, Hoddah H, Carbone E (2008) Calcium channels in chromaffin cells: focus on L and T types. Acta Physiol 192:233–246Google Scholar
  92. 92.
    Marcantoni A, Vandael DHF, Mahapatra S, Carabelli V, Sinnegger-Brauns MJ, Striessnig J, Carbone E (2010) Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. J Neurosci 30:491–504Google Scholar
  93. 93.
    Marrion NV, Tavalin SJ (1998) Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature 395:900–905Google Scholar
  94. 94.
    Martinez-Espinosa PL, Yang C, Gonzalez-Perez V, Xia XM, Lingle CJ (2014) Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity. J Gen Physiol 144:275–295Google Scholar
  95. 95.
    Marty A (1981) Ca-dependent K channels with large unitary conductance in chromaffin cell membranes. Nature 291:497–500Google Scholar
  96. 96.
    Marty A, Neher E (1985) Potassium channels in cultured bovine adrenal chromaffin cells. J Physiol 367:117–141Google Scholar
  97. 97.
    Neely A, Lingle CJ (1992) Effects of muscarine on single rat adrenal chromaffin cells. J Physiol 453:133–166Google Scholar
  98. 98.
    Neely A, Lingle CJ (1992) Two components of calcium-activated potassium current in rat adrenal chromaffin cells. J Physiol 453:97–131Google Scholar
  99. 99.
    Novara M, Baldelli P, Cavallari D, Carabelli V, Giancippoli A, Carbone E (2004) Exposure to cAMP and beta-adrenergic stimulation recruits Cav3 T-type channels in rat chromaffin cells through Epac cAMP-receptor proteins. J Physiol 558:433–449Google Scholar
  100. 100.
    O’Farrell M, Marley PD (1999) Different contributions of voltage-sensitive Ca2+ channels to histamine-induced catecholamine release and tyrosine hydroxylase activation in bovine adrenal chromaffin cells. Cell Calcium 25:209–217Google Scholar
  101. 101.
    Olivos L, Artalejo AR (2007) Muscarinic excitation-secretion coupling in chromaffin cells. Acta Physiol 192:213–220Google Scholar
  102. 102.
    Padin JF, Fernandez-Morales JC, de Diego AM, Garcia AG (2015) Calcium channel subtypes and exocytosis in chromaffin cells at early life. Curr Mol Pharmacol 8:81–86Google Scholar
  103. 103.
    Park YB (1994) Ion selectivity and gating of small conductance Ca2+-activated K+ channels in cultured rat adrenal chromaffin cells. J Physiol 481:555–570Google Scholar
  104. 104.
    Perez-Alvarez A, Hernandez-Vivanco A, Caba-Gonzalez JC, Albillos A (2011) Different roles attributed to Cav1 channel subtypes in spontaneous action potential firing and fine tuning of exocytosis in mouse chromaffin cells. J Neurochem 116:105–121Google Scholar
  105. 105.
    Perez-Alvarez A, Hernandez-Vivanco A, Cano-Abad M, Albillos A (2008) Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells. Pflügers Arch Eur J Physiol 456:1149–1162Google Scholar
  106. 106.
    Platzer J, Engel J, Schrott-Fischer A, Stephan K, Bova S, Chen H, Zheng H, Striessnig J (2000) Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102:89–97Google Scholar
  107. 107.
    Prakriya M, Lingle CJ (1999) BK channel activation by brief depolarizations requires Ca2+ influx through L- and Q-type Ca2+ channels in rat chromaffin cells. J Neurophysiol 81:2267–2278Google Scholar
  108. 108.
    Role LW, Perlman RL (1983) Both nicotinic and muscarinic receptors mediate catecholamine secretion by isolated guinea-pig chromaffin cells. Neuroscience 10:979–985Google Scholar
  109. 109.
    Rosa JM, Gandia L, Garcia AG (2009) Inhibition of N and PQ calcium channels by calcium entry through L channels in chromaffin cells. Pflügers Arch Eur J Physiol 458:795–807Google Scholar
  110. 110.
    Rush AM, Wittmack EK, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG (2006) Differential modulation of sodium channel Nav1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily. Eur J Neurosci 23:2551–2562Google Scholar
  111. 111.
    Scharinger A, Eckrich S, Vandael DH, Schonig K, Koschak A, Hecker D, Kaur G, Lee A, Sah A, Bartsch D, Benedetti B, Lieb A, Schick B, Singewald N, Sinnegger-Brauns MJ, Carbone E, Engel J, Striessnig J (2015) Cell-type-specific tuning of Cav1.3 Ca2+-channels by a C-terminal automodulatory domain. Front Cell Neurosci 9:18Google Scholar
  112. 112.
    Schmich RM, Miller MI (1997) Stochastic threshold characterization of the intensity of active channel dynamical action potential generation. J Neurophysiol 78:2616–2630Google Scholar
  113. 113.
    Schneidman E, Freedman B, Segev I (1998) Ion channel stochasticity may be critical in determining the reliability and precision of spike timing. Neural Comput 10:1679–1703Google Scholar
  114. 114.
    Scott RS, Bustillo D, Olivos-Oré LA, Cuchillo-Ibanez I, Barahona MV, Carbone E, Artalejo AR (2011) Contribution of BK channels to action potential repolarisation at minimal cytosolic Ca2+ concentration in chromaffin cells. Pflügers Arch Eur J Physiol 462:545–557Google Scholar
  115. 115.
    Shanley LJ, O’Malley D, Irving AJ, Ashford ML, Harvey J (2002) Leptin inhibits epileptiform-like activity in rat hippocampal neurones via PI3-kinase-driven activation of BK channels. J Physiol 545:933–944Google Scholar
  116. 116.
    Shukla R, Wakade AR (1991) Functional aspects of calcium channels of splanchnic neurons and chromaffin cells of the rat adrenal medulla. J Neurochem 56:753–758Google Scholar
  117. 117.
    Solaro CR, Lingle CJ (1992) Trypsin-sensitive, rapid inactivation of a calcium-activated potassium channel. Science 257:1694–1698Google Scholar
  118. 118.
    Solaro CR, Prakriya M, Ding JP, Lingle CJ (1995) Inactivating and noninactivating Ca2+- and voltage-dependent K+ current in rat adrenal chromaffin cells. J Neurosci 15:6110–6123Google Scholar
  119. 119.
    Sun L, Xiong Y, Zeng X, Wu Y, Pan N, Lingle CJ, Qu A, Ding J (2009) Differential regulation of action potentials by inactivating and noninactivating BK channels in rat adrenal chromaffin cells. Biophys J 97:1832–1842Google Scholar
  120. 120.
    Tamura R, Nemoto T, Maruta T, Onizuka S, Yanagita T, Wada A, Murakami M, Tsuneyoshi I (2014) Up-regulation of Nav1.7 sodium channels expression by tumor necrosis factor-α in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons. Anesth Analg 118:318–324Google Scholar
  121. 121.
    Thiagarajan R, Tewolde T, Li Y, Becker PL, Rich MM, Engisch KL (2003) Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells. J Physiol 555:439–457Google Scholar
  122. 122.
    Twitchell WA, Pena TL, Rane SG (1997) Ca2+-dependent K+ channels in bovine adrenal chromaffin cells are modulated by lipoxygenase metabolites of arachidonic acid. J Membr Biol 158:69–75Google Scholar
  123. 123.
    Twitchell WA, Rane SG (1994) Nucleotide-independent modulation of Ca2+-dependent K+ channel current by a μ-type opioid receptor. Mol Pharmacol 46:793–798Google Scholar
  124. 124.
    Twitchell WA, Rane SG (1993) Opioid peptide modulation of Ca2+-dependent K+ and voltage-activated Ca2+ currents in bovine adrenal chromaffin cells. Neuron 10:701–709Google Scholar
  125. 125.
    Van Goor F, Li YX, Stojilkovic SS (2001) Paradoxical role of large-conductance calcium-activated K+ (BK) channels in controlling action potential-driven Ca2+ entry in anterior pituitary cells. J Neurosci 21:5902–5915Google Scholar
  126. 126.
    Van Goor F, Zivadinovic D, Stojilkovic SS (2001) Differential expression of ionic channels in rat anterior pituitary cells. Mol Endocrinol 15:1222–1236Google Scholar
  127. 127.
    Vandael DH, Mahapatra S, Calorio C, Marcantoni A, Carbone E (2013) Cav1.3 and Cav1.2 channels of adrenal chromaffin cells: emerging views on cAMP/cGMP-mediated phosphorylation and role in pacemaking. Biochim Biophys Acta 1828:1608–1618Google Scholar
  128. 128.
    Vandael DH, Marcantoni A, Carbone E (2015) Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. Curr Mol Pharmacol 8:149–161Google Scholar
  129. 129.
    Vandael DH, Marcantoni A, Mahapatra S, Caro A, Ruth P, Zuccotti A, Knipper M, Carbone E (2010) Cav1.3 and BK channels for timing and regulating cell firing. Mol Neurobiol 42:185–198Google Scholar
  130. 130.
    Vandael DH, Ottaviani MM, Legros C, Lefort C, Guerineau NC, Allio A, Carabelli V, Carbone E (2015) Reduced availability of voltage-gated sodium channels by depolarization or blockade by tetrodotoxin boosts burst firing and catecholamine release in mouse chromaffin cells. J Physiol 593:905–927Google Scholar
  131. 131.
    Vandael DHF, Zuccotti A, Striessnig J, Carbone E (2012) Cav1.3-driven SK Channel activation regulates pacemaking and spike frequency adaptation in mouse chromaffin cells. J Neurosci 32:16345–16359Google Scholar
  132. 132.
    Vijayaragavan K, O’Leary ME, Chahine M (2001) Gating properties of Nav1.7 and Nav1.8 peripheral nerve sodium channels. J Neurosci 21:7909–7918Google Scholar
  133. 133.
    Wada A, Wanke E, Gullo F, Schiavon E (2008) Voltage-dependent Nav1.7 sodium channels: multiple roles in adrenal chromaffin cells and peripheral nervous system. Acta Physiol 192:221–231Google Scholar
  134. 134.
    Wada A, Yanagita T, Yokoo H, Kobayashi H (2004) Regulation of cell surface expression of voltage-dependent Nav1.7 sodium channels: mRNA stability and posttranscriptional control in adrenal chromaffin cells. Front Biosci 9:1954–1966Google Scholar
  135. 135.
    Wallace DJ, Chen C, Marley PD (2002) Histamine promotes excitability in bovine adrenal chromaffin cells by inhibiting an M-current. J Physiol 540:921–939Google Scholar
  136. 136.
    Wallner M, Meera P, Toro L (1999) Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog. Proc Natl Acad Sci U S A 96:4137–4142Google Scholar
  137. 137.
    Wang Y-W, Ding JP, Xia X-M, Lingle CJ (2002) Consequences of the stoichiometry of Slo1 α and auxiliary β subunits on functional properties of BK-type Ca2+-activated K+ channels. J Neurosci 22:1550–1561Google Scholar
  138. 138.
    Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD (2004) Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci 24:6765–6775Google Scholar
  139. 139.
    Womack MD, Chevez C, Khodakhah K (2004) Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J Neurosci 24:8818–8822Google Scholar
  140. 140.
    Xia X-M, Ding JP, Lingle CJ (1999) Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. J Neurosci 19:5255–5264Google Scholar
  141. 141.
    Xia XM, Ding JP, Lingle CJ (2003) Inactivation of BK channels by the NH2 terminus of the β2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues. J Gen Physiol 121:125–148Google Scholar
  142. 142.
    Zamponi GW, Currie KP (2013) Regulation of Cav2 calcium channels by G protein coupled receptors. Biochim Biophys Acta 1828:1629–1643Google Scholar
  143. 143.
    Zhang Q, Chibalina MV, Bengtsson M, Groschner LN, Ramracheya R, Rorsman NJ, Leiss V, Nassar MA, Welling A, Gribble FM, Reimann F, Hofmann F, Wood JN, Ashcroft FM, Rorsman P (2014) Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. J Physiol 592:4677–4696Google Scholar
  144. 144.
    Zhao J, O’Leary ME, Chahine M (2011) Regulation of Nav1.6 and Nav1.8 peripheral nerve Na+ channels by auxiliary beta-subunits. J Neurophysiol 106:608–619Google Scholar
  145. 145.
    Zhou Z, Misler S (1995) Action potential-induced quantal secretion of catecholamines from rat adrenal chromaffin cells. J Biol Chem 270:3498–3505Google Scholar
  146. 146.
    Zhou Z, Neher E (1993) Calcium permeability of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells. Pflügers Arch Eur J Physiol 425:511–517Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of AnesthesiologyWashington University School of Medicine in St. LouisSt.LouisUSA
  2. 2.Department of Drug Science, Laboratory of Cellular and Molecular Neuroscience, N.I.S. CentreTorinoItaly

Personalised recommendations