Calcium antagonistic drugs differ in ability to block the slow Na+ channels of young embryonic chick hearts.
Young (3-day-old) embryonic chick hearts have slowly rising action potentials (APs) dependent on slow Na+ channels, and these slow APs are blocked by verapamil, but not by Mn2+ (1 mM). In contrast, old embryonic hearts possess slow Ca2+-Na+ channels which can be blocked by both verapamil and Mn2+. In the present experiments, we compared the effects of a number of Ca antagonistic drugs on the spontaneous APs recorded from intact 3-day-old embryonic chick hearts (ventricles). At 10(-5) M, verapamil, D-600, and nifedipine abolished the spontaneous APs (3 X 10(-6) M produced some depression of Vmax). Electrical stimulation did not elicit APs, and long-duration hyperpolarizing pulses (applied because the maximum diastolic potential was moderately decreased) did not allow APs to be elicited by stimulation. This blockade was not reversed by elevation of [Ca]0 from 0.6 mM (control concentration used to reduce contractions) to 3.6 mM or 5.4 mM. However, lowering of [Na]0 from 137 mM to 68.5 mM facilitated the blockade. Washout of the drugs for 30 min produced nearly complete recovery. In contrast to the effects of verapamil, D-600, and nifedipine, 10(-5) M diltiazem, bepridil, and mesudipine had little or no depressant effect on Vmax; the same was true for 1 mM Mn2+. These results indicate that verapamil, D-600, and nifedipine are blockers of slow Na+ channels (as well as of slow Ca2+-Na+ channels), whereas diltiazem, bepridil and mesudipine do not block slow Na+ channels. Therefore, the Ca antagonistic drugs vary in their ability to block slow Na+ channels.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002642:Chick Embryo; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D005711:Gallopamil; D012964:Sodium; D014700:Verapamil; D009543:Nifedipine