Electropharmacological effects of a new dihydropyridine analog on isolated guinea pig papillary muscles and Purkinje fibers.
The effects of a new dihydropyridine, FR-34235, were compared with those of the dihydropyridine, nifedipine, and verapamil on the normal fast action potentials (APs), slow APs, and contractions of guinea pig papillary muscles and Purkinje fibers. FR-34235 (10(-6) M) blocked the contractions of papillary muscles superfused with normal Tyrode solution within 10-12 min. Maximal upstroke velocity (+Vmax) and overshoot of the fast APs were not affected, whereas the AP durations at 50 and 90% repolarization (APD50 and APD90) were shortened. The effects of FR-34235 on the fast APs and contractions were reversed within 10 min on washout. To determine the effects of the calcium antagonists on slow APs, the fast Na+ channels were inactivated by partial depolarization (to approximately -45 mV) by elevated [K]0, and isoproterenol (10(-6) M) or histamine (10(-5) M) was used to induce slow APs on stimulation. Nifedipine (10(-7) M) and verapamil (2 X 10(-6) M) completely blocked the slow APs. FR-34235 depressed (3 X 10(-8) M) and blocked (10(-7) M) the slow APs in a frequency-dependent manner. The effects were reversed by elevated [Ca]0 or washout of the drug. The contractions accompanying the slow APs were depressed and blocked in parallel with the depression of +Vmax. In guinea pig Purkinje fibers, FR-34235 had no significant effect on the fast AP parameters but produced a marked depression of automaticity. FR-34235 also blocked the slow APs of the Purkinje fibers in a frequency-dependent manner; all drug effects were reversed within 10 min on washout.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006633:Histamine Antagonists; C035100:nilvadipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D007545:Isoproterenol