THE ROLE OF NA-CA2+ EXCHANGE CURRENT IN ELECTRICAL RESTITUTION IN FERRET VENTRICULAR CELLS()

1. The mechanisms underlying electrical restitution (recovery of actio n potential duration after a preceding beat) were investigated in ferr et ventricular cells. The time to 80 % recovery (t(80)) of action pote ntial duration was similar to 204 ms. 2. At a holding potential of -80 mV, the Ca2+ current (I-Ca) reactivated and the delayed rectifier Kcurrent (I-K) deactivated very rapidly (t(80): similar to 32 and simil ar to 93 ms, respectively). The kinetics of both currents are too fast to account for electrical restitution alone. 3. The putative inward N a+-Ca2+ exchange current (INa-Ca) produced by the Na+-Ca2+ exchanger i n response to the intrracellular Ca2+ transient reprimed (t(80): 189 m s) with the same time course as mechanical restitution (recovery of co ntraction) and with a similar time course to electrical restitution. 4 . Substantial reduction of inward INa-Ca, by buffering intracellular C a2+ with the acetyl methyl ester form of BAPTA, shortened the action p otential and greatly altered the electrical restitution curve. Subsequ ent addition of nifedipine (to block I-Ca) or 4-aminopyridine (4-AP) ( to block the transient outward current, I-TO) further altered the elec trical restitution curve. 5. Any time-dependent current that contribut es to the action potential is likely to affect the time course of elec trical restitution. Although I-Ca, I-K and I-TO were previously though t to be the only currents involved in electrical restitution, we concl ude that inward INa-Ca also plays an important role.