Contractility of the heart as a function of sarcolemmal calcium handling.

Our previously published results suggest that contractile heart function may now be thought of in terms of calcium handling by the myocardial cells. We postulate that upon depolarisation the sarcolemma releases calcium bound to the inner leaflet which diffuses to the contractile proteins to control contraction. This calcium is taken up upon relaxation by intracellular binding sites, including sarcoplasmic reticulum. Upon repolarisation, some of this calcium is reaccumulated by the sarcolemma with a time course of approximately 500 ms. When this interval is allowed, the contractility of any beat, C, was found experimentally to be a function of that of the preceding beat, Cp, and of the duration of the preceding action potential, APDp, according to the multiple regression analysis: C = Bc X Cp + Ba(APDp - D). Bc is the fraction of calcium released on beat Cp which recirculates to beat C. The remainder is expelled and balanced in the steady state by calcium entry during the action potentials. The calcium influx from a given action potential (APDp) is not released until the subsequent beat (C). This calcium only enters during the latter half of the action potential, the first half being "dead time" (D). We speculate that the calcium entry channel is not specific for calcium but is inhibited by calcium bound to the inner leaflet of the sarcolemma. The channel is "opened" when this calcium is released upon depolarisation. The initial current is carried by sodium ions and subsequent calcium entry leads to reinhibition of the channel.