The late component of L-type calcium current during guinea-pig cardiac action potentials and its contribution to...

L-Type Ca2+ current (ICa,L) elicited during the action potential (AP) of guinea-pig ventricular myocytes exhibits an early and a late component. The whole-cell patch-clamp technique was used to characterize the process regulating the late ICa,L component and to assess its contribution to excitation-contraction coupling. A stepwise decrease in repolarization rate of AP-like voltage-clamp pulses led to an exponential increase in Ca2+ charge carried by ICa, L. This saturation behaviour was significantly reduced or absent when Ba2+ or monovalent cations were used as charge carriers, which suggests that the late component of ICa,L is controlled mainly by Ca2+-dependent processes. Simultaneously recording ICa,L and zero-load shortening or the internal Ca2+ concentration (fura-2) revealed that Ca2+ carried by the late component of ICa,L markedly contributes to the Ca2+ content of the sarcoplasmic reticulum (SR). Reducing the charge transfer by late ICa,L during a series of AP-like conditioning clamp pulses by 48% reduced the shortening amplitude during a subsequent test stimulation by 56%. This relationship was absent during long rectangular depolarizing conditioning clamps, during which Na+/Ca2+ exchange increased its influence on SR Ca2+ loading. The late component of ICa,L developed only a minor direct influence on the simultaneous cell shortening. Thus, the main contribution of the late ICa,L component is to supply Ca2+ for SR loading.