EFFECTS OF ANTIISCHEMIC DRUGS ON VERATRIDINE-INDUCED HYPERCONTRACTURE IN RAT CARDIAC MYOCYTES

The effects of different groups of substances (beta-adrenoceptor antagonists, Ca2+ channel blockers and vasodilators) which are known to have antiischemic properties were studied on veratridine-induced hypercontracture. Veratridine increases Na+ influx by slowing the inactivation process of the Na+ channel, thereby inducing a continuously increased Na+ entry in depolarized cells. Veratridine (6.3 x 10(-6) M) produced a change in cell shape from rod-shape to round; resulting from hypercontracture of cells. Before treatment with veratridine the proportion of rod-shaped cells was 70% and fell to 0% 5 min after the treatment with veratridine. dl-Propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep all inhibited veratridine-induced hypercontracture dose dependently. In contrast, acebutolol, atenolol, timolol, nifedipine, diltiazem, and nitroglycerin did not inhibit the rounding of cells. Concomitantly with the rounding of cells, the [Ca2+](i) was increased by veratridine. dl-Propranolol, d-propranolol and dilazep prevented the increase of [Ca2+](i) induced by veratridine, whereas timolol and nitroglycerin did not. These results show that dl-propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep possess Na+ channel blocking actions on the veratridine-modified Na+ channel, thereby preventing excessive Na+ influx and secondary Ca2+ overload.