Skip to main content
SpringerLink
Log in

ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hypoxia-induced shortening of the action potential duration, attributed to activation of the ATP-sensitive potassium (KATP) channels, occurs to a much greater extent in ventricular cells from diabetic rats. This study examined whether the KATP channels are altered in streptozotocin-diabetic myocardium. In inside-out patches from ventricular myocytes (with symmetrical 140 mM [K+]), inward KATP currents (at potentials negative to the K+ reversal potential) were similar in amplitude in control and diabetic patches (slope conductances: 69 and 74 pS, respectively). However, outward single-channel currents were larger for channels from diabetic heart cells than from control cells (e.g., at +75 mV the diabetic channel currents were 3.7 ± 0.3 pA vs. 2.7 ± 0.1 pA for control currents, p < 0.05), due to reduced inward rectification of diabetic channel currents. There was no difference in open and closed times between control and diabetic channels. The IC50 for ATP inhibition of the KATP channel single-channel currents was 11.4 μM for control currents and 4.7 μM for diabetic channel currents. Thus, the major difference found between KATP channels from control and diabetic hearts was the greater outward diabetic single-channel current, which may contribute to the enhanced sensitivity to hypoxia (or ischemia) in diabetic hearts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Noma A: ATP-regulated K1 channels in cardiac muscle. Nature 305: 147–148, 1983

    Article  CAS  PubMed  Google Scholar 

  2. Trube G, Hescheler J: Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cellattached patches. Pfluegers Arch 401: 178–184, 1984

    Article  CAS  Google Scholar 

  3. Fosset M, De Weille JR, Green RD, Schmid-Antomarchi H, Lazdunski M: Antidiabetic sulphonylureas control action potential duration in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels. J Biol Chem 263: 7933–7936, 1988

    Article  CAS  PubMed  Google Scholar 

  4. Nichols CG, Ripoll C, Lederer WJ: ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction. Circ Res 68: 280–287, 1991

    Article  CAS  PubMed  Google Scholar 

  5. Aomine M, Nobe S, Arita M: Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats. Diabetes 39: 1485–1489, 1990

    Article  CAS  PubMed  Google Scholar 

  6. Arena JP, Kass RS: Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel. Circ Res 65: 436–445, 1989

    Article  CAS  PubMed  Google Scholar 

  7. Escande D, Thuringer D, Le Guern S, Courteix J, Laville M, Cavero I: Potassium channel openers act through activation of ATP-sensitive K−channels in guinea-pig cardiac myocytes. Pfluegers Arch 414: 669–675, 1989

    Article  CAS  Google Scholar 

  8. Paulson DJ, Matthews R, Bowman J, Zhao J: Metabolic effects of treadmill exercise training on the diabetic heart. J Appl Physiol 73: 265–271, 1992

    Article  CAS  PubMed  Google Scholar 

  9. Wahler GM, Sperelakis N: New Ca21 agonist (Bay K 8644) enhances and induces cardiac slow action potentials. Am J Physiol 247: H337-H340, 1984

    CAS  PubMed  Google Scholar 

  10. Wahler GM: Developmental increases in the inwardly-rectifying potassium current in the rat heart. Am J Physiol 262: C1266–01272, 1992

    Article  CAS  PubMed  Google Scholar 

  11. Powell T: Methods for the isolation and preparation of single adult myocytes. In: W.A. Clark, R.S. Decker, T.K. Borg (eds). Biology of Isolated Adult Cardiac Myocytes. Elsevier Press, New York, 1988, pp 9–13

    Google Scholar 

  12. Yazawa K, Kaibara M, Ohara M, Kameyama M: An improved method for isolating cardiac myocytes useful for patch-clamp studies. Japan J Physiol 40: 157–163, 1990

    Article  CAS  Google Scholar 

  13. Zilberter Y, Burnashev N, Papin A, Portnov V, Khodorov B: Gating kinetics of ATP-sensitive single potassium channels in myocardial cells depends on electromotive force. Pfluegers Arch 411: 584–589, 1988

    Article  CAS  Google Scholar 

  14. Findlay I: ATP-sensitive K+ channels in rat ventricular myocytes are blocked and inactivated by internal divalent cations. Pfluegers Arch 410: 313–320, 1987

    Article  CAS  Google Scholar 

  15. Kozlowski RZ, Ashford MLJ: ATP-sensitive K+ channel run-down is Mg2+ dependent. Proc R Soc Lond 240: 397–410, 1990

    CAS  PubMed  Google Scholar 

  16. Nichols CG, Lederer WJ: The regulation of ATP-sensitive K+ channel activity in intact and permeabilized rat ventricular myocytes. J Physiol (Lond) 423: 91–110, 1990

    Article  CAS  Google Scholar 

  17. Bruning JL, Kintz BL: Computational Handbook of Statistics. Scott, Foresman and Company, Glenview, IL, 1987

    Google Scholar 

  18. Jourdon P, Feuvray D: Calcium and potassium currents in ventricular myocytes isolated from diabetic rats. J Physiol 470: 411–429, 1993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang DW, Kiyosue K, Shigematsu S, Arita M: Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes. Am J Physiol 269: H1288-H1296, 1995

    CAS  PubMed  Google Scholar 

  20. Kannell WB: Role of diabetes in cardiac disease: conclusions from population studies. In: S. Zonaraich (ed.). Diabetes and the Heart Thomas Publishers, Springfield, IL, 1978, pp 97–112

  21. Hearse DJ, Steward DA, Chain EB: Diabetes and the survival and recovery of the anoxic myocardium. J Molec Cell Cardiol 7: 397–415, 1975

    Article  CAS  Google Scholar 

  22. Feuvray D, Idell-Wenger JR, Neely JR: Effects of ischemia on rat myocardial function and metabolism in diabetics. Circ Res 44: 322–329, 1979

    Article  CAS  PubMed  Google Scholar 

  23. Ingebretsen CG, Moreau P, Hawelu-Johnson C, Ingebretsen WR Jr: Performance of diabetic rat hearts: effects of anoxia and increased work. Am J Physiol 239: H614-H620, 1980

    CAS  PubMed  Google Scholar 

  24. Tani M, Neely JR: Hearts from diabetic rats are more resistant to in vitro ischemia: possible role of altered Ca2+ metabolism. Circ Res 62: 931–940, 1988

    Article  CAS  PubMed  Google Scholar 

  25. Dillmann WH: Diabetes and thyroid-hormone-induced changes in cardiac function and their molecular basis. Ann Rev Med 40: 373–394, 1989

    Article  CAS  PubMed  Google Scholar 

  26. Fein FS, Aronson RS, Nordin B, Miller-Green B, Sonnenblick EH: Altered myocardial response to ouabain in diabetic rats: mechanics and electrophysiology. J Molee Cell Cardiol 15: 769–784, 1983

    Article  CAS  Google Scholar 

  27. Sauviat MP, Feuvray D: Electrophysiological analysis of the sensitivity to calcium in ventricular muscle from alloxan diabetic rats. Basic Res Cardiol 81: 489–496, 1986

    Article  CAS  PubMed  Google Scholar 

  28. Nobe S, Aomine M, Arita M, Ito S, Takaki R: Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: circumstantial evidence for impaired Ca2+ channel. Cardiovasc Res 24: 381–389, 1990

    Article  CAS  PubMed  Google Scholar 

  29. Cameron JS, Baghdady R: Role of ATP sensitive potassium channels in long term adaptation to metabolic stress. Cardiovas Res 28: 788–796, 1988

    Article  Google Scholar 

  30. Janse MJ, Wit AL: Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69: 1049–1169, 1989

    Article  CAS  PubMed  Google Scholar 

  31. Lee SL, Ostadalova I, Kolar F, Dhalla NS: Alterations in Ca2+ channels during the development of diabetic cardiomyopathy. Mol Cell Biochem 109: 173–179, 1992

    CAS  PubMed  Google Scholar 

  32. Shimoni Y, Firek L, Severson D, Giles W: Short-term diabetes alters K− currents in rat ventricular myocytes. Circ Res 74: 620–628, 1994

    Article  CAS  PubMed  Google Scholar 

  33. Arena JP, Kass RS: Activation of ATP-sensitive K− channels in heart cells by pinacidil: dependence on ATP. Am J Physiol 257: H2092-H2096, 1989

    CAS  PubMed  Google Scholar 

  34. Martin CL, Chinn K: Pinacidil opens ATP-dependent K+ channels in cardiac myocytes in an ATP- and temperature-dependent manner. J Cardiovasc Pharmacol 15: 510–514, 1990

    Article  CAS  PubMed  Google Scholar 

  35. Nakayama K, Fan Z, Marumo F, Hiraoka M: Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATPsensitive K− current in guinea pig ventricular myocytes. Circ Res 67: 1124–1133, 1990

    Article  CAS  PubMed  Google Scholar 

  36. Allison TB, Bruttig SP, Cross MF, Eliot RS, Shipp JC: Reduced high energy phosphate levels in rat hearts. I. Effects of alloxan diabetes. Am J Physiol 230: 1744–1750, 1976

    Article  CAS  PubMed  Google Scholar 

  37. Weiss JN, Lamp ST: Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis. J Gen Physiol 94: 911–934, 1989

    Article  CAS  PubMed  Google Scholar 

  38. Nakagawa M, Kobayashi S, Kimura I, Kimura M: Diabetic state induced modification of Ca, Mg, Fe and Zn content of skeletal, cardiac and smooth muscles. Endocrin Japan 36: 795–807, 1989

    Article  CAS  Google Scholar 

  39. Undrovinas AI, Bumashev N, Eroshenko D, Fleidervish I, Starmer CF, Makielski JC, Rosenshtraukh LV: Quinidine blocks the adenosine 5′-triphosphate-sensitive potassium channels in heart. Am J Physiol 2509: H1609-H1612, 1990

    Google Scholar 

  40. Gopalakrishnan M, Janis RA, Triggle DJ: ATP-sensitive K+ channels: Pharmacologic properties, regulation and therapeutic potential. Drug Dev Res 28: 95–127, 1993

    Article  CAS  Google Scholar 

  41. Findlay I: ATP4 and ATP-Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes. Pfluegers Arch 412: 37–41, 1988

    Article  CAS  Google Scholar 

  42. Lederer WJ, Nichols CG: Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches. J Physiol (Lond) 419: 193–211, 1989

    Article  CAS  Google Scholar 

  43. Findlay I: Calcium-dependent inactivation of the ATP-sensitive K+ channel of rat ventricular myocytes. Biochim Biophys Acta 943: 297–304, 1988

    Article  CAS  PubMed  Google Scholar 

  44. Cameron JS, Kimura S, Jackson-Burns DA, Smith DB, Bassett AL: ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes. Am J Physiol 255: H1254-H1258, 1988

    CAS  PubMed  Google Scholar 

  45. Horie M, Irisawa H, Noma A: Voltage-dependent magnesium block of adenosine-triphosphate-sensitive potassium channel in guinea-pig ventricular cells. J Physiol 387: 251–272, 1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mayhan W, Faraci FM: Responses of cerebral arterioles in diabetic rats to activation of ATP-sensitive potassium channels. Am J Physiol 265: H152-H157, 1993

    CAS  PubMed  Google Scholar 

  47. Kamata K, Miyata N, Kasuya Y: Functional changes in potassium channels in aortas from rats with streptozotocin-induced diabetes. Europ J Pharmacol 166: 319–323, 1989

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Midwestern University, 60515, Downers Grove, IL

    Jacquelyn M. Mitra & Gordon M. Wahler

  2. Department of Physiology and Biophysics, University of Illinois at Chicago, 60612, Chicago, IL, USA

    Gordon M. Wahler

  3. Department of Physiology, Midwestern University, 60515, Downers Grove, IL, USA

    Gordon M. Wahler

Authors
  1. Jacquelyn M. Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gordon M. Wahler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitra, J.M., Wahler, G.M. ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats. Mol Cell Biochem 158, 43–51 (1996). https://doi.org/10.1007/BF00225881

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00225881

Key words

Search

Navigation