Rate-dependent prolongation of action potential duration in isolated rat ventricular myocytes

Rate-dependent alterations of action potential duration (APD) in rat ventricular myocytes were investigated. Action potentials of the isolated myocytes were recorded with patch electrodes containing EGTA (11 mM), and showed a marked rate-dependent prolongation in the APD (0.2-5 Hz). This prolongation was significantly inhibited in the presence of 4-aminopyridine (4-AP), a blocker of the transient outward K+ current (Ito). Thus, the rate-dependent decrease in Ito may underlie the change in APD. In contrast, the action potentials recorded from rat ventricular papillary muscles with conventional microelectrodes did not show rate-dependent alterations in the APD, i.e., the APD remained practically unaltered at the frequency range of 0.2-5 Hz. These results suggest that the rate-dependent prolongation of APD (due to rate-dependent blockade of Ito) becomes evident when the intracellular Ca2+ was chelated by the internal application of EGTA via patch pipette. We speculate that the rate-dependent prolongation of APD (via decreases in Ito) is masked in the ventricular papillary muscles, probably due to rate-dependent decreases in the inward current (e.g., electrogenic Na(+)-Ca2+ exchange current) that is regulated by the intracellular calcium.