Ionic basis of myocardial contractility.
Knowledge about the basic physiology of mammalian cardiac muscle has lagged behind that of skeletal muscle because the tissue is more difficult to deal with experimentally. The cells are much smaller, they do not tolerate anaerobic conditions very well, and they cannot be tentanized. Therefore as knowledge has developed about skeletal muscle, there has been a tendency to extrapolate to the myocardium. In many instances such extrapolation has been misleading especially in the area of ionic control of contractility. The mammalian heart, with its "all or none" contraction, must have an intrinsic mode of modulating its force development. There is no mechanism as in skeletal muscle for recruitment of more or less motor units as force or work required varies. The heart cell uses two basic mechanisms in the regulation of its contraction--the variation of force with initial cellular length (the classic Frank-Starling mechanism) and the variation of the amount of Ca that reaches the myofilaments. This brief review has focused on the second mechanism. I have emphasized the following points: 1. The source of contractile-dependent Ca in the heart is at the cell surface in rapid equilibrium with the extracellular space. 2. It is likely that a large portion of this surface Ca is bound to negatively charged molecules located in the surface coat/external lamina complex. Sialic acid is a major constituent of the surface complex and recent studies indicate that it is important in the control of Ca permeability in the myocardial cell. 3. The Ca derived from the surface complex crosses the sarcolemmal unit membrane by two routes: (a) a "pore" system: passage through this system is electrogenic and measurable by voltage-clamp technique; (b) a "carrier system": passage through this system is coupled to the outward movement of another cation--most likely Na--such that it is electroneutral and therfore, the inward Ca movements are not detectable by voltage-clamp technique. 4. The primary action of the digitalis glycosides is to inhibit the Na-K pump. This increases Na intracellularly, which in turn increases the Na-Ca carrier activity with the result that more Ca is delivered to the myofilaments. This produces the well-known positive inotropic effect. 5. Finally, there remains considerable controversy with respect to the foregoing points. At this time, they should be viewed as components of a working model that awaits the development of experimental tools to test further its validity.
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004071:Digitalis Glycosides / Q000494:pharmacology*; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012794:Sialic Acids / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D013268:Stimulation, Chemical
D004071:Digitalis Glycosides; D012794:Sialic Acids; D010042:Ouabain; D012964:Sodium; D011188:Potassium; D002118:Calcium