Cytoskeletal actin microfilaments and the transient outward potassium current in hypertrophied rat ventriculocytes.

The durations of transmembrane action potentials recorded from single myocytes isolated from the endocardial surface of hypertrophied left ventricles of rats were increased, compared to the durations recorded from normal left ventricular cells at 36-37 degrees C. Exposure to phalloidin (1-20 microM, < 20 min), a specific stabilizer of the non-myofibrillar actin microfilament component of the cardiac cytoskeleton, had no effect on action potential duration of normal cells, but significantly shortened the prolonged action potentials of hypertrophied cells. Cytochalasin D (5-50 microM), a disrupter of the actin microfilaments, also had little effect on action potential duration of normal cells. However, cytochalasin D further increased the action potential duration of hypertrophied cells at 10 min exposure. The addition of phalloidin to solutions containing cytochalasin D, reduced the latter's increase of action potential duration in hypertrophied cells. Whole-cell transient outward K(+) current (I(to1)) density was significantly decreased in hypertrophied cells. At a test potential of +60 mV, the mean I(to1) density recorded from normal cells was 13.5 +/- 1.1 pA pF(-1) (n = 18) compared to 4.17 +/- 1.2 pA pF(-1) for LVH cells (n = 22; P < 0.05). Phalloidin (20 microM) increased and cytochalasin D (50 microM) decreased whole-cell I(to1) in hypertrophied cells but had no effect on I(to1), in normal cells. When equimolar concentrations were used, phalloidin, 10 microM, reversed the decrease in I(to1) brought about by cytochalasin D, 10 microM, in hypertrophied cells. The L-type calcium current density was reduced in LVH compared to normal cells. Phalloidin (20 microM) and cytochalasin D (50 microM) had no effect on I(Ca,L) in normal or LVH myocytes. The decrease in I(to1) in hypertrophied cells and the altered I(to1) responsiveness to phalloidin and cytochalasin D reflect modification of I(to1) channel function mediated, in part, through hypertrophy-altered cytoskeletal actin microfilament regulation of I(to1).