Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Muscarinic receptor-mediated increase of intracellular Na+-ion activity and force of contraction

  • 28 Accesses

  • 71 Citations

Abstract

The aim of the present study was to determine the mechanism of the positive inotropic effect of carbachol on ventricular myocardium. Carbachol produced a concentration-dependent (0.1 to 300 μmol/l) increase in contraction force on the catecholamine-depleted papillary muscle of the guinea pig without affecting the normal action potential or the slow action potential evoked in 24 mmol/l K+. Since atropine prevented the inotropic effect of carbachol, muscarinic receptors were involved. Carbachol (300 μmol/l) produced an increase in intracellular Na+-ion-activity,a Na i , by about 3 mmol/l in the quiescent muscle, and the time course of thea Na i change corresponded with the development of the positive inotropic effect as determined in the stimulated preparation (0.2 Hz). The effect of carbachol on force of contraction and ona Na i was diminished by reducing [Ca2+]0. The positive inotropic effect of carbachol was dependent on repetitive activity and was markedly enhanced in the presence of dihydro-ouabain. The results are consistent with the hypothesis, that carbachol increases the Na+ permeability of the sarcolemma via muscarinic receptors, and enhances force of contraction by stimulating the Na+−Ca2+-exchange.

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

References

  1. Berridge MJ (1984) Inositol triphosphate and diacylglycerol as second messengers. Biochem J 220:345–360

  2. Biegon RL, Epstein PM, Pappano AJ (1980) Muscarinic antagonism of the effects of a phosphodiesterase inhibitor (methylisobutylxantine) in embryonic chick ventricle. J Pharmacol Exp Ther 215:348–356

  3. Blinks JR (1966) Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J Pharmacol Exp Ther 151:221–235

  4. Brady AJ (1967) Physiological appraisal of the actions of catecholamines on myocardial contractions. Ann NY Acad Sci 139:661–672

  5. Buccino RA, Sonnenblick EH, Cooper T, Braunwald E (1966) Direct positive inotropic effect of acetylcholine on myocardium. Circ Res 19:1097–1108

  6. Cohen CJ, Fozzard HA, Sheu S-S (1982) Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle. Circ Res 50:651–662

  7. Ebner F, Reiter M (1977) The dependence on contraction frequency of the positive inotropic effect of dihydro-ouabain. Naunyn-Schmiedeberg's Arch Pharmacol 300:1–9

  8. Eisner DA, Lederer WJ (1979) The role of the sodium pump in the effects of potassium-depleted solutions on mammalian cardiac muscle. J Physiol (Lond) 294:279–301

  9. Eisner DA, Lederer WJ, Vaughan-Jones RD (1983) The control of tonic tension by membrane potential and intracellular sodium activity in the sheep cardiac Purkinje fibre. J Physiol (Lond) 335:723–743

  10. Ellis D (1977) The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J Physiol (Lond) 273:211–240

  11. Endoh M, Tamura K, Hashimoto K (1970) Negative and positive inotropic responses of the blood-perfused canine papillary muscle to acetylcholine. J Pharmacol Exp Ther 175:377–387

  12. Friedman WF, Buccino RA, Sonnenblick EH, Braunwald E (1967) Effects of frequency of contraction and ionic environment on the response of heart muscle to acetylcholine. Circ Res 21:573–582

  13. Harned HS, Robinson RA (1968) Multicomponent electrolyte solutions. Pergamon Press, Oxford

  14. Hermsmeyer K, Sperelakis N (1970) Decrease in K+ conductance and depolarization of frog cardiac muscle produced by Ba2+. Am J Physiol 219:1108–1114

  15. Higgins CB, Vatner SF, Braunwald E (1973) Parasympathetic control of the heart. Pharmacol Rev 25:119–155

  16. Hino N, Ochi R (1980) Effect of acetylcholine on membrane currents in guinea-pig papillary muscle. J Physiol (Lond) 307:183–197

  17. Hoffman BF, Suckling EE (1953) Cardiac cellular potentials: effect of vagal stimulation and acetylcholine. Am J Physiol 173:312–320

  18. Lee CO, Dagostino M (1982) Effect of strophanthidin on intracellular Na ion activity and twitch tension of constantly driven canine cardiac Purkinje fibers. Biophys J 40:185–198

  19. Lee CO, Vassalle M (1983) Modulation of intracellular Na+ activity and cardiac force by norepinephrine and Ca2+. Am J Physiol 244 (Cell Physiol 13):C110-C114

  20. MacInnes DA (1981) The principles of electrochemistry. Dover Publications Inc, New York

  21. Mullins LJ (1981) Ion transport in heart. Raven Press, New York

  22. Muscholl E (1970) Cholinomimetic drugs and release of the adrenergic transmitter. In: New aspects of storage and release mechanisms of catecholamines. Springer, Berlin Heidelberg New York, pp 168–186

  23. Ochi R (1981) Decrease in calcium conductance by acetylcholine in mammalian ventricular muscle. In: The mechanism of gated calcium transport across biological membranes. Academic Press, New York, pp 79–86

  24. Pitzer KS, Mayorga G (1973) Thermodynamics of electrolytes. II. Activity and osmotic coefficients for strong electrolytes with one or both ions univalent. J Phys Chem 27:2300–2308

  25. Reiter M (1967) Die Wertbestimmung inotrop wirkender Arzneimittel am isolierten Papillarmuskel. Arzneimittelforsch 17:1249–1253

  26. Reuter H, Seitz N (1968) The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol (Lond) 195:451–470

  27. Sheu S-S, Fozzard HA (1982) Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development. J Gen Physiol 80:325–351

  28. Steiner RA, Oehme M, Ammann D, Simon W (1979) Neutral carrier sodium ion-selective microelectrodes for intracellular studies. Analyt Chem 51:351–353

  29. Thomas RC (1978) Ion-sensitive intracellular microelectrodes. Academic Press, New York

  30. Wasserstrom JA, Schwartz DJ, Fozzard HA (1983) Relation between intracellular sodium and twitch tension in sheep cardiac Purkinje strands exposed to cardiac glycosides. Circ Res 52:697–705

Download references

Author information

Correspondence to Michael Korth.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Korth, M., Kühlkamp, V. Muscarinic receptor-mediated increase of intracellular Na+-ion activity and force of contraction. Pflugers Arch. 403, 266–272 (1985). https://doi.org/10.1007/BF00583598

Download citation

Key words

  • Muscarinic receptor
  • Carbachol
  • Positive inotropic effect
  • Intracellular Na+-ion-activity
  • Guinea-pig papillary muscle