Influence of N-ethylmaleimide on action potential and force of contraction of guinea-pig papillary muscles.

1. Standard microelectrode techniques were used to investigate the influence of N-ethylmaleimide on the action potential, slow response action potential and force of contraction of guinea-pig papillary muscles. 2. N-ethylmaleimide, 3 x 10(-5) to 10(-4) mol l-1, concentration-dependently increased the force of contraction. The positive inotropic effect developed quickly and, with the largest drug concentration, was followed by a progressive decline of the contractile force. The action potential duration was progressively shortened by N-ethylmaleimide. 3. The effects of N-ethylmaleimide were not prevented in the presence of tetrodotoxin 3 x 10(-8) mol l-1 and propranolol 4 x 10(-6) mol l-1 or by a reduction of the Na(+)-concentration to 70 mmol l-1. 4. Verapamil, 10(-6) mol l-1, reduced the positive inotropic, but not the action potential shortening effect of N-ethylmaleimide. 5. In K(+)-depolarized muscles in the presence of propranolol and tetrodotoxin, N-ethylmaleimide 10(-4) mol l-1 increased the maximum depolarization velocity and the duration of the slow response action potential. The latter effect was transient and was followed by a progressive reduction of the action potential duration. 6. The most likely explanation for the action potential shortening effect of N-ethylmaleimide seems to be an increase of an outward potassium current while the transient inotropic effect of the drug may be caused, at least in part, by an increase of the slow inward calcium current.