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)
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology
D012433:Ryanodine; D000001:Calcimycin; D011899:Ranitidine; D010869:Pindolol; D009543:Nifedipine; D002118:Calcium