Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1988 May;399:519–535. doi: 10.1113/jphysiol.1988.sp017094

Indirect effects of acetylcholine on the electrogenic sodium pump in bull-frog atrial muscle fibres.

H Hasuo 1, K Koketsu 1, S Minota 1
PMCID: PMC1191678  PMID: 2457093

Abstract

1. Effects of acetylcholine (ACh) on the activity of electrogenic Na+ pump in bullfrog atrial muscle fibres were examined using the single sucrose-gap voltage clamp technique. 2. In the K+-free solution, 10 microM-ACh induced a large outward current (ACh-induced current) with an increase in the membrane conductance. 3. The amplitude of the ACh-induced current decreased to 15% of the control 10 min after application of 1 microM-ouabain, suggesting the contribution of electrogenic Na+ pump to the ACh-induced current. The remaining ACh-induced current was not affected even if the concentration of ouabain was increased ten times. 4. The K+-activated current induced by an activation of the electrogenic Na+ pump was suppressed or reversed its direction during the course of the ACh-induced current. 5. The ACh-induced current was completely inhibited by applications of either atropine or barium ions while the K+-activated current was not affected. 6. Both ouabain-sensitive and -insensitive ACh-induced currents were decreased when the membrane was hyperpolarized and eliminated around -95 mV. 7. The ouabain-sensitive component was decreased by increasing the external K+ concentration [K+]o; the proportions of this current to ACh-induced current in 0.5, 0.75, 1 and 2 mM [K+]o were 54, 42, 34 and 14%, respectively. 8. The current-voltage (i-v) relation obtained in 2 or 4 mM [K+]o, where the currents carried by Na+ and Ca2+ were blocked by application of 1 microM-TTX and 1 mM-Cd2+, exhibits marked inward-going rectification but does not show a clear N-shaped feature. Ba2+ (1 mM) induced an inward current at the holding potential (-80 mV) and eliminated the inward-going rectification of the membrane. 9. These results suggest that the increase in the K+ permeability by ACh increases the concentration of K+ immediately outside of the membrane, which in turn stimulates the electrogenic Na+ pump mechanism. The physiological significance of the action of ACh on the electrogenic Na+ pump in bull-frog atrium is discussed in relation to the background K+ current (IK,1).

Full text

PDF
519

Selected References

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

  1. Akasu T., Ohta Y., Koketsu K. The effect of adrenaline on the electrogenic Na+ pump in cardiac muscle cells. Experientia. 1978 Apr 15;34(4):488–490. doi: 10.1007/BF01935944. [DOI] [PubMed] [Google Scholar]
  2. Akera T., Brody T. M. Myocardial membranes: regulation and function of the sodium pump. Annu Rev Physiol. 1982;44:375–388. doi: 10.1146/annurev.ph.44.030182.002111. [DOI] [PubMed] [Google Scholar]
  3. Argibay J. A., Dutey P., Ildefonse M., Ojeda C., Rougier O., Tourneur Y. Block by Cs of K current iK1 and of carbachol induced K current iCch in frog atrium. Pflugers Arch. 1983 Jun 1;397(4):295–299. doi: 10.1007/BF00580264. [DOI] [PubMed] [Google Scholar]
  4. Beeler G. W., Jr, Reuter H. Voltage clamp experiments on ventricular myocarial fibres. J Physiol. 1970 Mar;207(1):165–190. doi: 10.1113/jphysiol.1970.sp009055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carmeliet E., Mubagwa K. Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibres. J Physiol. 1986 Feb;371:201–217. doi: 10.1113/jphysiol.1986.sp015969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Carmeliet E., Ramon J. Effect of acetylcholine on time-independent currents in sheep cardiac Purkinje fibers. Pflugers Arch. 1980 Sep;387(3):207–216. doi: 10.1007/BF00580972. [DOI] [PubMed] [Google Scholar]
  8. Colatsky T. J., Tsien R. W. Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres. J Physiol. 1979 May;290(2):227–252. doi: 10.1113/jphysiol.1979.sp012769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DUDEL J., TRAUTWEIN W. Die Wirkung von Adrenalin auf das Ruhepotential von Myokardfasern des Vorhofs. Experientia. 1956 Oct 15;12(10):396–398. doi: 10.1007/BF02157290. [DOI] [PubMed] [Google Scholar]
  10. Daut J., Rüdel R. The electrogenic sodium pump in guinea-pig ventricular muscle: inhibition of pump current by cardiac glycosides. J Physiol. 1982 Sep;330:243–264. doi: 10.1113/jphysiol.1982.sp014339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eisner D. A., Lederer W. J. Characterization of the electrogenic sodium pump in cardiac Purkinje fibres. J Physiol. 1980 Jun;303:441–474. doi: 10.1113/jphysiol.1980.sp013298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gadsby D. C. Activation of electrogenic Na+/K+ exchange by extracellular K+ in canine cardiac Purkinje fibers. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4035–4039. doi: 10.1073/pnas.77.7.4035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gadsby D. C. Beta-adrenoceptor agonists increase membrane K+ conductance in cardiac Purkinje fibres. Nature. 1983 Dec 15;306(5944):691–693. doi: 10.1038/306691a0. [DOI] [PubMed] [Google Scholar]
  14. Gadsby D. C., Kimura J., Noma A. Voltage dependence of Na/K pump current in isolated heart cells. Nature. 1985 May 2;315(6014):63–65. doi: 10.1038/315063a0. [DOI] [PubMed] [Google Scholar]
  15. Gadsby D. C. The Na/K pump of cardiac cells. Annu Rev Biophys Bioeng. 1984;13:373–398. doi: 10.1146/annurev.bb.13.060184.002105. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Giles W. R., Shibata E. F. Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents. J Physiol. 1985 Nov;368:265–292. doi: 10.1113/jphysiol.1985.sp015857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Glitsch H. G. Activation of the electrogenic sodium pump in guinea-pig auricles by internal sodium ions. J Physiol. 1972 Feb;220(3):565–582. doi: 10.1113/jphysiol.1972.sp009723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Glitsch H. G. Electrogenic Na pumping in the heart. Annu Rev Physiol. 1982;44:389–400. doi: 10.1146/annurev.ph.44.030182.002133. [DOI] [PubMed] [Google Scholar]
  21. Glitsch H. G., Grabowski W., Thielen J. Activation of the electrogenic sodium pump in guinea-pig atria by external potassium ions. J Physiol. 1978 Mar;276:515–524. doi: 10.1113/jphysiol.1978.sp012250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hasuo H., Koketsu K. Potential dependency of the electrogenic Na+-pump current in bullfrog atrial muscles. Jpn J Physiol. 1985;35(1):89–100. doi: 10.2170/jjphysiol.35.89. [DOI] [PubMed] [Google Scholar]
  23. Hume J. R., Giles W. Ionic currents in single isolated bullfrog atrial cells. J Gen Physiol. 1983 Feb;81(2):153–194. doi: 10.1085/jgp.81.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Isenberg G., Trautwein W. The effect of dihydro-ouabain and lithium-ions on the outward current in cardiac Purkinje fibers. Evidence for electrogenicity of active transport. Pflugers Arch. 1974;350(1):41–54. doi: 10.1007/BF00586737. [DOI] [PubMed] [Google Scholar]
  25. Kameyama M., Kiyosue T., Soejima M. Single channel analysis of the inward rectifier K current in the rabbit ventricular cells. Jpn J Physiol. 1983;33(6):1039–1056. doi: 10.2170/jjphysiol.33.1039. [DOI] [PubMed] [Google Scholar]
  26. Kimura J., Noma A., Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature. 1986 Feb 13;319(6054):596–597. doi: 10.1038/319596a0. [DOI] [PubMed] [Google Scholar]
  27. Kurachi Y., Noma A., Irisawa H. Electrogenic sodium pump in rabbit atrio-ventricular node cell. Pflugers Arch. 1981 Oct;391(4):261–266. doi: 10.1007/BF00581504. [DOI] [PubMed] [Google Scholar]
  28. Mechmann S., Pott L. Identification of Na-Ca exchange current in single cardiac myocytes. Nature. 1986 Feb 13;319(6054):597–599. doi: 10.1038/319597a0. [DOI] [PubMed] [Google Scholar]
  29. Minota S., Koketsu K. Activation of the electrogenic Na-pump of cardiac muscle fibres by ACh in K-free solutions. Experientia. 1979 Jun 15;35(6):772–773. doi: 10.1007/BF01968238. [DOI] [PubMed] [Google Scholar]
  30. Mubagwa K., Carmeliet E. Effects of acetylcholine on electrophysiological properties of rabbit cardiac Purkinje fibers. Circ Res. 1983 Dec;53(6):740–751. doi: 10.1161/01.res.53.6.740. [DOI] [PubMed] [Google Scholar]
  31. Noma A., Irisawa H. Contribution of an electrogenic sodium pump to the membrane potential in rabbit sinoatrial node cells. Pflugers Arch. 1975 Aug 12;358(4):289–301. doi: 10.1007/BF00580527. [DOI] [PubMed] [Google Scholar]
  32. Noma A., Irisawa H. Electrogenic sodium pump in rabbit sinoatrial node cell. Pflugers Arch. 1974;351(2):177–182. doi: 10.1007/BF00587436. [DOI] [PubMed] [Google Scholar]
  33. Noma A., Nakayama T., Kurachi Y., Irisawa H. Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit. Jpn J Physiol. 1984;34(2):245–254. doi: 10.2170/jjphysiol.34.245. [DOI] [PubMed] [Google Scholar]
  34. Noma A., Peper K., Trautwein W. Acetylcholine-induced potassium current fluctuations in the rabbit sino-atrial node. Pflugers Arch. 1979 Sep;381(3):255–262. doi: 10.1007/BF00583257. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Ojeda C., Rougier O., Tourneur Y. Effects of Cs on acetylcholine induced current. Is ik1 increased by acetylcholine in frog atrium? Pflugers Arch. 1981 Jul;391(1):57–59. doi: 10.1007/BF00580695. [DOI] [PubMed] [Google Scholar]
  37. Osterrieder W., Yang Q. F., Trautwein W. Effects of barium on the membrane currents in the rabbit S-A node. Pflugers Arch. 1982 Jul;394(1):78–84. doi: 10.1007/BF01108311. [DOI] [PubMed] [Google Scholar]
  38. PAGE E., STORN S. R. CAT HEART MUSCLE IN VITRO. 8. ACTIVE TRANSPORT OF SODIUM IN PAPILLARY MUSCLES. J Gen Physiol. 1965 May;48:957–972. doi: 10.1085/jgp.48.5.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sakmann B., Noma A., Trautwein W. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature. 1983 May 19;303(5914):250–253. doi: 10.1038/303250a0. [DOI] [PubMed] [Google Scholar]
  40. Sakmann B., Trube G. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol. 1984 Feb;347:659–683. doi: 10.1113/jphysiol.1984.sp015089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. TRAUTWEIN W., DUDEL J. Zum Mechanismus der Membranwirkung des Acetylcholin an der Herzmuskelfaser. Pflugers Arch. 1958;266(3):324–334. doi: 10.1007/BF00416781. [DOI] [PubMed] [Google Scholar]
  43. TRAUTWEIN W., SCHMIDT R. F. [On the membrane effect of adrenalin on the myocardial fiber]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;271:715–726. [PubMed] [Google Scholar]
  44. 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]
  45. Vassalle M., Barnabei O. Norepinephrine and potassium fluxes in cardiac Purkinje fibers. Pflugers Arch. 1971;322(4):287–303. doi: 10.1007/BF00587747. [DOI] [PubMed] [Google Scholar]

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

RESOURCES