Events at the cardiac sarcolemma: localization and movement of contractile-dependent calcium

At present there is a controversy about the appropriate model for excitation-contraction (E-C) coupling in mammalian heart muscle. There is an apparent conflict between the data derived from voltage clamp experiments and data derived from isotopic exchange studies. The maximum transsarcolemmal Ca influx as derived from voltage clamp studies is not more than 10 mumoles/kg wet weight heart per beat. This is barely enough to achieve 10% activation of contractile force. It has been proposed, therefore, that the remainder of the required Ca is derived from intracellular sites. However, ionic exchange studies, using specific E-C uncouplers such as lanthanum, indicate that the major source of coupling Ca is external to the sarcolemma. Its movement, during E-C coupling, would then have to be nonelectrogenic since influx of this quantity of Ca is not discerned with voltage clamp experiments. It is proposed that on excitation, Ca moves across the cardiac sarcolemma by two routes: 1) a small amount through a pore or channel and 2) a much larger amount via an electroneutral carrier. Movement through the pore would be electrogenic and therefore measurable with the voltage clamp whereas movement via the carrier would not be evident with the clamp. The model is consistent with the proposal that the immediate source of contractile-dependent Ca in mammalian heart is derived from sites external to the sarcolemmal (and T tubular) membrane.