Rate-dependent changes in action potential duration and membrane currents in hamster ventricular myocytes

Abstract

Hamsters are frequently studied as a model of cardiomyopathy, but the electrophysiological properties of a hamster heart are not well defined. We examined rate-dependent changes in action potentials and underlying ionic mechanisms in isolated ventricular myocytes from hamster hearts using the whole-cell configuration of the patch clamp technique. At 0.1 Hz stimulation, the mean action potential duration at 90% (APD₉₀) and 20% (APD₂₀) repolarization were 63±7  ms and 9±1 ms, respectively (n=17). With increasing frequency of stimulation, APD progressively prolonged to 119±16 ms (APD₉₀) and 36±7 ms (APD₂₀) at 6.0 Hz. A further increase in the rate of stimulation to 8.0 Hz did not change APD significantly. Application of 4 mM 4-aminopyridine (4-AP) lengthened APD markedly and completely prevented the rate-dependent prolongation. Cd²⁺ (0.2 mM) shortened APD and generally attenuated the rate-dependent lengthening of APD up to 5.0 Hz, but unaffected the lengthening of APD with the further increase in the rate. At plateau voltages, there were two time-dependent currents, I _to1 and I _Ca,L. Recovery from inactivation for I _to1 had two components: t _slow=980±129 ms accounting for 58% of the total fraction, and t _fast=39±13 ms (n=7). Recovery from inactivation for I _Ca,L was rapid with t=20±4 ms (n=6). Results suggest that the slow recovery from inactivation in I _to1 is the main reason for the rate-dependent prolongation of APD in hamster ventricular myocytes.