CA2-POTENTIAL IN GUINEA-PIG VENTRICULAR MYOCYTES( INFLUX DURING THE CARDIAC ACTION)

The relative contributions of L-type Ca2+ current (I-Ca) and Na+/Ca2exchange to Ca2+ influx during the cardiac action potential (AP) are u nknown. In this study, we have used an AP recorded under physiological conditions as the command voltage applied to voltage-clamped ventricu lar myocytes. I-Ca (measured as nifedipine-sensitive membrane current) had a complex multiphasic time course during the AP. Peak I-Ca was ty pically 4 pA/pF, after which it rapidly declined (to about 60% of peak ) during the rising phase of the cell-wide Ca2+ transient before incre asing to a second, more sustained component. The initial decline in I- Ca was sensitive to the amount of Ca2+ released by the sarcoplasmic re ticulum (SR), and conditions that reduce the amplitude of the Ca2+ tra nsient (such as rest or brief application of caffeine) increased net C a2+ influx via I-Ca Dissection of the Na+/Ca2+ exchange current at the start of the AP suggested that Ca2+ influx via Na+/Ca2+ exchange is l ess than 30% of that due to I-Ca. From these data, we suggest that I-C a is the primary source of Ca2+ that triggers SR Ca2+ release, even al the highly depolarized membrane potentials associated with the AP. Ho wever, Ca2+ influx via Na+/Ca2+ exchange is not negligible and may act ivate some Ca2+ release from the SR, especially when Ic, is reduced. W e propose that SR Ca2+ release inhibits I-Ca within the same beat, the reby providing a negative feedback mechanism that may serve to limit C a2+ influx as well as to regulate the amount of Ca2+ stored within the SR.