Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1987 Aug;389:411–422. doi: 10.1113/jphysiol.1987.sp016663

Comparison of effects of acetylcholine on calcium and potassium currents in frog atrium and ventricle.

H C Hartzell 1, M A Simmons 1
PMCID: PMC1192087  PMID: 2445977

Abstract

1. Ca2+ and K+ currents were measured in single atrial and ventricular myocytes from frog heart with the whole-cell patch-clamp technique. 2. K+ currents were blocked with intra- and extracellular Cs+ and the fast Na+ current was blocked with tetrodotoxin (TTX). The Ca2+ current (ICa) was evoked by a depolarizing pulse from -80 to 0 mV. ICa was larger in ventricular (3.4 +/- 2.5 microA/cm2) than atrial (1.6 +/- 2.5 microA/cm2) myocytes. 3. Acetylcholine (ACh) had no effect on basal ICa when K+ currents were blocked with Cs+ or Ba2+. Isoprenaline increased ICa and ACh reduced the isoprenaline-stimulated current to basal levels. 4. In contrast, when K+ currents were not blocked, ACh reduced the net inward current and increased the outward current at the end of the depolarizing pulse. The outward current was studied in the presence of Cd2+ to block ICa. The steady-state current-voltage relationship inwardly rectified and reversed near the K+ reversal potential (EK). The magnitude of the steady-state ACh-activated K+ current at 0 mV was 1.0 +/- 0.7 microA/cm2 in ventricular cells and 3.67 +/- 1.7 microA/cm2 in atrial cells. 5. With depolarization, the outward current increased instantaneously and then decreased to a new steady level. The first phase of the decay occurred with a time constant similar to that of the activation of ICa. The Cd2+-sensitive current (corresponding to ICa) was obtained by subtracting currents in the presence and absence of Cd2+. The Cd2+-sensitive current was not affected by ACh. 6. The apparent effect of ACh on basal ICa can be explained quantitatively by activation of a time-dependent K+ current by ACh that contaminates ICa.

Full text

PDF
411

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoni H., Rotmann M. Zum Mechanismus der negative inotropen Acetylcholin-Wirkung auf das isolierte Froschmyokard. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;300(2):67–86. [PubMed] [Google Scholar]
  2. Biegon R. L., Pappano A. J. Dual mechanism for inhibition of calcium-dependent action potentials by acetylcholine in avian ventricular muscle. Relationship to cyclic AMP. Circ Res. 1980 Mar;46(3):353–362. doi: 10.1161/01.res.46.3.353. [DOI] [PubMed] [Google Scholar]
  3. Carmeliet E., Mubagwa K. Characterization of the acetylcholine-induced potassium current in rabbit cardiac Purkinje fibres. J Physiol. 1986 Feb;371:219–237. doi: 10.1113/jphysiol.1986.sp015970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chapman R. A. Excitation-contraction coupling in cardiac muscle. Prog Biophys Mol Biol. 1979;35(1):1–52. doi: 10.1016/0079-6107(80)90002-4. [DOI] [PubMed] [Google Scholar]
  5. Fischmeister R., Hartzell H. C. Cyclic guanosine 3',5'-monophosphate regulates the calcium current in single cells from frog ventricle. J Physiol. 1987 Jun;387:453–472. doi: 10.1113/jphysiol.1987.sp016584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fischmeister R., Hartzell H. C. Mechanism of action of acetylcholine on calcium current in single cells from frog ventricle. J Physiol. 1986 Jul;376:183–202. doi: 10.1113/jphysiol.1986.sp016148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Flitney F. W., Singh J. Evidence that cyclic GMP may regulate cyclic AMP metabolism in the isolated frog ventricle. J Mol Cell Cardiol. 1981 Nov;13(11):963–979. doi: 10.1016/0022-2828(81)90472-7. [DOI] [PubMed] [Google Scholar]
  8. Garnier D., Nargeot J., Ojeda C., Rougier O. The action of acetylcholine on background conductance in frog atrial trabeculae. J Physiol. 1978 Jan;274:381–396. doi: 10.1113/jphysiol.1978.sp012154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Giles W., Noble S. J. Changes in membrane currents in bullfrog atrium produced by acetylcholine. J Physiol. 1976 Sep;261(1):103–123. doi: 10.1113/jphysiol.1976.sp011550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  11. Hartzell H. C. Distribution of muscarinic acetylcholine receptors and presynaptic nerve terminals in amphibian heart. J Cell Biol. 1980 Jul;86(1):6–20. doi: 10.1083/jcb.86.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartzell H. C., Fischmeister R. Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells. Nature. 1986 Sep 18;323(6085):273–275. doi: 10.1038/323273a0. [DOI] [PubMed] [Google Scholar]
  13. Hino N., Ochi R. Effect of acetylcholine on membrane currents in guinea-pig papillary muscle. J Physiol. 1980 Oct;307:183–197. doi: 10.1113/jphysiol.1980.sp013430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Iijima T., Irisawa H., Kameyama M. Membrane currents and their modification by acetylcholine in isolated single atrial cells of the guinea-pig. J Physiol. 1985 Feb;359:485–501. doi: 10.1113/jphysiol.1985.sp015598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ikemoto Y., Goto M. Effects of ACh on slow inward current and tension components of the bullfrog atrium. J Mol Cell Cardiol. 1977 Apr;9(4):313–326. doi: 10.1016/s0022-2828(77)80037-0. [DOI] [PubMed] [Google Scholar]
  16. Inoue D., Hachisu M., Pappano A. J. Acetylcholine increases resting membrane potassium conductance in atrial but not in ventricular muscle during muscarinic inhibition of Ca++-dependent action potentials in chick heart. Circ Res. 1983 Aug;53(2):158–167. doi: 10.1161/01.res.53.2.158. [DOI] [PubMed] [Google Scholar]
  17. Josephson I., Sperelakis N. On the ionic mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle. J Gen Physiol. 1982 Jan;79(1):69–86. doi: 10.1085/jgp.79.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Keely S. L., Jr, Lincoln T. M., Corbin J. D. Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase. Am J Physiol. 1978 Apr;234(4):H432–H438. doi: 10.1152/ajpheart.1978.234.4.H432. [DOI] [PubMed] [Google Scholar]
  19. Kurachi Y., Nakajima T., Sugimoto T. Acetylcholine activation of K+ channels in cell-free membrane of atrial cells. Am J Physiol. 1986 Sep;251(3 Pt 2):H681–H684. doi: 10.1152/ajpheart.1986.251.3.H681. [DOI] [PubMed] [Google Scholar]
  20. Linden J., Brooker G. The questionable role of cyclic guanosine 3':5'-monophosphate in heart. Biochem Pharmacol. 1979 Dec 1;28(23):3351–3360. doi: 10.1016/0006-2952(79)90072-8. [DOI] [PubMed] [Google Scholar]
  21. McAfee D. A., Whiting G. J., Siegel B. Neurotransmitter and cyclic nucleotide modulation of frog cardiac contractility. J Mol Cell Cardiol. 1978 Aug;10(8):705–716. doi: 10.1016/0022-2828(78)90405-4. [DOI] [PubMed] [Google Scholar]
  22. Morad M., Goldman Y. E., Trentham D. R. Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart. Nature. 1983 Aug 18;304(5927):635–638. doi: 10.1038/304635a0. [DOI] [PubMed] [Google Scholar]
  23. Nargeot J., Garnier D. The action of muscarinic agonists and antagonists on frog atrial fibers. Electrophysiological studies. J Pharmacol. 1982 Jul-Sep;13(3):431–445. [PubMed] [Google Scholar]
  24. New W., Trautwein W. The ionic nature of slow inward current and its relation to contraction. Pflugers Arch. 1972;334(1):24–38. doi: 10.1007/BF00585998. [DOI] [PubMed] [Google Scholar]
  25. Noma A., Trautwein W. Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell. Pflugers Arch. 1978 Nov 30;377(3):193–200. doi: 10.1007/BF00584272. [DOI] [PubMed] [Google Scholar]
  26. Pfaffinger P. J., Martin J. M., Hunter D. D., Nathanson N. M., Hille B. GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature. 1985 Oct 10;317(6037):536–538. doi: 10.1038/317536a0. [DOI] [PubMed] [Google Scholar]
  27. Richard S., Nerbonne J. M., Nargeot J., Lester H. A., Garnier D. Photochemically produced intracellular concentration jumps of cAMP mimic the effects of catecholamines on excitation-contraction coupling in frog atrial fibers. Pflugers Arch. 1985 Mar;403(3):312–317. doi: 10.1007/BF00583606. [DOI] [PubMed] [Google Scholar]
  28. Simmons M. A., Creazzo T., Hartzell H. C. A time-dependent and voltage-sensitive K+ current in single cells from frog atrium. J Gen Physiol. 1986 Dec;88(6):739–755. doi: 10.1085/jgp.88.6.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Soejima M., Noma A. Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch. 1984 Apr;400(4):424–431. doi: 10.1007/BF00587544. [DOI] [PubMed] [Google Scholar]
  30. Ten Eick R., Nawrath H., McDonald T. F., Trautwein W. On the mechanism of the negative inotropic effect of acetylcholine. Pflugers Arch. 1976 Feb 24;361(3):207–213. doi: 10.1007/BF00587284. [DOI] [PubMed] [Google Scholar]
  31. Watanabe A. M., Besch H. R., Jr Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium. Circ Res. 1975 Sep;37(3):309–317. doi: 10.1161/01.res.37.3.309. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES