UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Excitation-contraction coupling in myocardium

Authors
Timothy W Smith, MD, PhD
James P Morgan, MD, PhD
Section Editor
Wilson S Colucci, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC

INTRODUCTION

Excitation-contraction (E-C) coupling refers to the series of events that link the action potential (excitation) of the muscle cell membrane (the sarcolemma) to muscular contraction. Although E-C coupling in myocardium is similar in many ways to skeletal muscle and smooth muscle, there are also critical differences. The cyclical nature of cardiac contraction and the importance of myocardial relaxation to cardiac pump function requires that any discussion of E-C coupling also consider the events terminating the muscle twitch as an integral part of the subject. Modulation of muscular function is said to affect inotropy (the speed and strength of muscular contraction) or lusitropy (the ability of the muscle to relax). Increased knowledge about E-C coupling has been a key to understanding both the inotropic and lusitropic states, and it continues to be useful in developing improved therapy for heart failure and cardiogenic shock.

This is a brief review of cardiac excitation (the myocardial action potential) followed by a description of muscular contraction. E-C coupling is then presented as the transduction of a membrane signal (the action potential) to an intracellular effector (the contractile apparatus) by way of a second messenger (intracellular free calcium [Ca2+]).

MYOCARDIAL ACTION POTENTIAL

The resting membrane potential of the myocardial cell is cell interior negative (-90 mV), and is primarily determined by the ratio of intracellular-to-extracellular potassium as predicted by the Nernst equation. The action potential is a temporary depolarization of the membrane. It is caused by transient changes in membrane conductance of several charged ions, especially sodium, due to the opening and closing of ion-specific channels in the membrane. This process can be summarized as follows (figure 1 and movie 1) [1]. (See "Myocardial action potential and action of antiarrhythmic drugs".)

Rapid depolarization (phase 0) occurs when the resting cell is brought to threshold, leading sequentially to activation or opening of voltage-dependent sodium channels, rapid sodium entry into the cells down a favorable concentration gradient, and a cell interior positive potential that can approach +45 mV. The marked depolarization results in voltage-dependent inactivation of the sodium channels and cessation of the inward sodium flux. Calcium channels also open during depolarization but the onset of the inward calcium flux is much slower.

Phase 1 repolarization is primarily due to inactivation of the sodium channels with abolition of the inward sodium current.

                 

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Dec 22 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Katz AM. Mechanism and control of the cardiac contractile process. In: Physiology of the Heart, Raven Press, New York 1992. p.178.
  2. Smith TW. Digitalis. Mechanisms of action and clinical use. N Engl J Med 1988; 318:358.
  3. Katz AM. Cyclic adenosine monophosphate effects on the myocardium: a man who blows hot and cold with one breath. J Am Coll Cardiol 1983; 2:143.
  4. Frank K, Kranias EG. Phospholamban and cardiac contractility. Ann Med 2000; 32:572.
  5. Scholz J, Schaefer B, Schmitz W, et al. Alpha-1 adrenoceptor-mediated positive inotropic effect and inositol trisphosphate increase in mammalian heart. J Pharmacol Exp Ther 1988; 245:327.
  6. Baker KM, Booz GW, Dostal DE. Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 1992; 54:227.
  7. Dzau VJ. Tissue renin-angiotensin system in myocardial hypertrophy and failure. Arch Intern Med 1993; 153:937.
  8. Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993; 75:977.
  9. Holubarsch C, Hasenfuss G, Schmidt-Schweda S, et al. Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. An in vitro study under physiological experimental conditions. Circulation 1993; 88:1228.
  10. Kaumann A, Bartel S, Molenaar P, et al. Activation of beta2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure. Circulation 1999; 99:65.
  11. Hoh JF, Rossmanith GH, Kwan LJ, Hamilton AM. Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis. Circ Res 1988; 62:452.
  12. Puceat M, Clement O, Lechene P, et al. Neurohormonal control of calcium sensitivity of myofilaments in rat single heart cells. Circ Res 1990; 67:517.
  13. Orchard CH, Kentish JC. Effects of changes of pH on the contractile function of cardiac muscle. Am J Physiol 1990; 258:C967.
  14. Poole-Wilson PA. Regulation of intracellular pH in the myocardium; relevance to pathology. Mol Cell Biochem 1989; 89:151.
  15. Solaro RJ, el-Saleh SC, Kentish JC. Ca2+, pH and the regulation of cardiac myofilament force and ATPase activity. Mol Cell Biochem 1989; 89:163.
  16. Gómez AM, Guatimosim S, Dilly KW, et al. Heart failure after myocardial infarction: altered excitation-contraction coupling. Circulation 2001; 104:688.
  17. Gwathmey JK, Copelas L, MacKinnon R, et al. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 1987; 61:70.
  18. Hobai IA, O'Rourke B. Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure. Circulation 2001; 103:1577.
  19. Morgan JP. Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 1991; 325:625.
  20. Grossman W. Diastolic dysfunction in congestive heart failure. N Engl J Med 1991; 325:1557.
  21. Soufer R, Wohlgelernter D, Vita NA, et al. Intact systolic left ventricular function in clinical congestive heart failure. Am J Cardiol 1985; 55:1032.
  22. Feldman MD, Copelas L, Gwathmey JK, et al. Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 1987; 75:331.
  23. Näbauer M, Böhm M, Brown L, et al. Positive inotropic effects in isolated ventricular myocardium from non-failing and terminally failing human hearts. Eur J Clin Invest 1988; 18:600.
  24. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991; 325:1468.
  25. Kubo SH, Gollub S, Bourge R, et al. Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group. Circulation 1992; 85:942.
  26. Feridooni HA, Dibb KM, Howlett SE. How cardiomyocyte excitation, calcium release and contraction become altered with age. J Mol Cell Cardiol 2015; 83:62.