Ca2+ influx during the cardiac action potential in guinea pig ventricular myocytes.

The relative contributions of L-type Ca2+ current (ICa) and Na+/Ca2+ exchange to Ca2+ influx during the cardiac action potential (AP) are unknown. In this study, we have used an AP recorded under physiological conditions as the command voltage applied to voltage-clamped ventricular myocytes. ICa (measured as nifedipine-sensitive membrane current) had a complex multiphasic time course during the AP. Peak ICa was typically 4 pA/pF, after which it rapidly declined (to about 60% of peak) during the rising phase of the cell-wide Ca2+ transient before increasing to a second, more sustained component. The initial decline in ICa was sensitive to the amount of Ca2+ released by the sarcoplasmic reticulum (SR), and conditions that reduce the amplitude of the Ca2+ transient (such as rest or brief application of caffeine) increased net Ca2+ influx via ICa. Dissection of the Na+/Ca2+ exchange current at the start of the AP suggested that Ca2+ influx via Na+/Ca2+ exchange is less than 30% of that due to ICa. From these data, we suggest that ICa is the primary source of Ca2+ that triggers SR Ca2+ release, even at the highly depolarized membrane potentials associated with the AP. However, Ca2+ influx via Na+/Ca2+ exchange is not negligible and may activate some Ca2+ release from the SR, especially when ICa is reduced. We propose that SR Ca2+ release inhibits ICa within the same beat, thereby providing a negative feedback mechanism that may serve to limit Ca2+ influx as well as to regulate the amount of Ca2+ stored within the SR.

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