Advertisement

Pflügers Archiv

, Volume 409, Issue 6, pp 582–588 | Cite as

Changes of membrane currents in cardiac cells induced by long whole-cell recordings and tolbutamide

  • B. Belles
  • J. Hescheler
  • G. Trube
Excitable Tissues and Central Nervous Physiology

Abstract

Single isolated myocytes were obtained from the ventricles of adult guinea pig hearts. The whole-cell recording configuration of the patch-clamp technique was used to measure membrane currents. A decrease (run-down) of the Ca2+ inward current and an increase of a time-independent K+ outward current were observed during long lasting (1–3 h) recordings. The time at which the outward current developed depended on the intracellular ATP concentration in the pipette, suggesting that this current is identical to the ATP-dependent K+ current described by Noma and Shibasaki (1985). However, the maximum outward current reached in the experiments was independent of the ATP concentration indicating a limited diffusion of ATP in the cell interior. In single-channel experiments on isolated patches of cell membrane and in whole-cell recordings the ATP-dependent K+ current could be blocked by the hypoglycaemic sulphonylurea tolbutamide. The IC50 of 0.38 mM was about 50 times higher than that reported for pancreatic β-cells (Trube et al. 1986). The Ca2+ inward current and the inwardly retifying K+ current were not affected by tolbutamide (3 mM).

Key words

Cardiac myocytes Ca2+ current ATP-dependent K+ current Run-down ATP Tolbutamide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bechem M, Pott L (1985) Removal of Ca current inactivation in dialysed guinea-pig atrial cardioballs by Ca chelators. Pflügers Arch 404:10–20Google Scholar
  2. Brown M, Lee KS, Powel T (1981) Voltage clamp and internal perfusion of single rat heart muscle cells. J Physiol 318:455–477Google Scholar
  3. Callewaert G, Vereecke J, Carmeliet E (1986) Existence of a calcium-dependent potassium channel in the membrane of cow cardiac Purkinje cells. Pflügers Arch 406:424–426Google Scholar
  4. Castle NA, Haylett DG (1987) Effect of channel blockers on potassium efflux from metabolically exhausted frog skeletal muscle. J Physiol 383:31–43Google Scholar
  5. Chad JE, Eckert R (1986) An enzymatic mechanism for calcium current inactivation in dialyzed helix neurones. J Physiol 378:31–51Google Scholar
  6. Cook DL, Hales N (1984) Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature 311:271–273Google Scholar
  7. Curtis GP, Setchfield J, Lucchesi BR (1975) The cardiac pharmacology of tolbutamide. J Pharmacol Exp Ther 194: 264–273Google Scholar
  8. Fenwick EM, Marty A, Neher E (1982) Sodium and calcium channels in bovine chromaffine cells. J Physiol 331:599–635Google Scholar
  9. Gylfe E, Hellman B, Sehlin J, Täljedal IB (1984) Interaction of sulfonylurea with the pancreatic B-cell. Experientia 40:1126–1134Google Scholar
  10. Hamill O, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100Google Scholar
  11. Hescheler J, Kameyama M, Trautwein W (1986) On the mechanism of muscarinic inhibition of cardiac Ca current. Pflügers Arch 407:182–189Google Scholar
  12. Isenberg G (1977) Cardiac Purkinje fibers. Ca2+ controls steady state potassium conductance. Pflügers Arch 371:71–76Google Scholar
  13. Isenberg G, Klöckner U (1982) Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium”. Pflügers Arch 395:6–18Google Scholar
  14. Jack JJB, Noble D, Tsien RW (1975) Electric current flow in excitable cells. Clarendon Press, OxfordGoogle Scholar
  15. Jackson JE, Bressler R (1981) Clinical pharmacology of sulfonylurca hypoglycaemic agents: part 1. Drugs 22:211–245Google Scholar
  16. Jones DP (1986) Intracellular diffusion gradients of O2 and ATP. Am J Physiol 250:C663-C675Google Scholar
  17. Kakei M, Noma A, Shibasaki T (1985) Properties of adenosinetriphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol 363:441–462Google Scholar
  18. Kameyama M, Hescheler J, Hofmann F, Trautwein W (1986a) Modulation of Ca current during the phosphorylation cycle in guinea pig heart. Pflügers Arch 407:123–128Google Scholar
  19. Kameyama M, Hescheler J, Mieskes G, Trautwein W (1986b) The protein-specific phosphatase 1 antagonizes the β-adrenergic increase of the cardiac Ca current. Pflügers Arch 407:461–463Google Scholar
  20. Kramer JH, Lampson WG, Schaffer SW (1983) Effect of tolbutamide on myocardial energy metabolism. Am J Physiol 245:H313-H319Google Scholar
  21. Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305:147–148Google Scholar
  22. Noma A, Shibasaki T (1985) Membrane current through adenosinetriphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol 363:463–480Google Scholar
  23. Ohno-Shosaku T, Zünkler BJ, Trube G (1987) Dual effects of ATP on K+ currents of mouse pancreatic β-cells. Pflügers Arch 408:133–138Google Scholar
  24. Rorsman P, Trube G (1985) Glucose dependent K+-channels in pancreatic β-cells are regulated by intracellular ATP. Pflügers Arch 405:305–309Google Scholar
  25. Saito K, Fukunaga H, Matuoka T, Birou S, Kashima T, Tanaka H (1986) Effects of tolbutamide on cultured heart cells of mice. J Mol Cell Cardiol 18:449–454Google Scholar
  26. Sturgess NC, Ashford MLJ, Cook DL, Hales CN (1985) The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet 8453:474–475Google Scholar
  27. Tan BH, Wilson GL, Schaffer SW (1984) Effect of tolbutamide on myocardial metabolism and mechanical performance of diabetic rat. Diabetes 33:1138–1143Google Scholar
  28. Trube G, Hescheler J (1984) Inward-rectifying channels in isolated patches of heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflügers Arch 401:178–184Google Scholar
  29. Trube G, Rorsman P, Ohno-Shosaku T (1986) Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic β-cells. Pflügers Arch 407:493–499Google Scholar
  30. University Group Diabetes Program (1970) A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 19, suppl. 2:787–830Google Scholar
  31. Zini R, d'Athis P, Hoareau A, Tillement JP (1976) Binding of four sulphonamides to human albumin. Europ J Clin Pharmacol 10:139–145Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • B. Belles
    • 1
  • J. Hescheler
    • 1
  • G. Trube
    • 2
  1. 1.II. Physiologisches InstitutUniversität des SaarlandesHomburg/SaarGermany
  2. 2.Max-Planck-Institut für biophysikalische ChemieGöttingenGermany

Personalised recommendations