Electromechanical effects of A23187 on guinea-pig ventricular muscle: a dual action of A23187.

The effects of A23187 on electromechanical activity of guinea-pig papillary muscles were examined by microelectrode techniques. A23187 (10(-6) M) caused a marked positive inotropic effect (868% of control) on preparations driven at 0.2 Hz. This inotropic effect was accompanied by a significant prolongation of the action potential duration at an early repolarization phase (APD 10), but not at a late repolarization phase (APD 30 and APD 80). Other parameters of action potential were unaffected. In the presence of nifedipine (10(-6) M), Ca2+ channel blocker, A23187 still increased the contractile force (495% of control) but had no effect on APD 10. On the other hand, APD 30 and APD 80 were significantly shortened. In the presence of ryanodine (2 X 10(-6) M), an inhibitor of internal Ca2+ release, A23187 was also able to cause the positive inotropic effect (389% of control). This inotropic effect was accompanied by a prolonged APD 10. These electrical and mechanical effects of A23187 were completely blocked by the combined treatment with nifedipine and ryanodine, suggesting that A23187 has a dual action. In papillary muscles depolarized by 26 mM [K+]0, A23187 augmented the slow action potential. In voltage clamp experiments using a single sucrose-gap method, A23187 caused a marked increase in the slow inward current and the outward current. The effects of A23187 were not antagonized by a beta-adrenoceptor and a histamine (H2) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)