Effects of calcium channel antagonists and facilitators on beating of primary cultures of embryonic chick heart cells.
1. Primary aggregate cultures of embryonic chick heart have been used to investigate the effects of calcium channel antagonists and facilitators on myocardial contractility. 2. The number of aggregates showing movement was inhibited in a concentration-dependent manner by calcium antagonists from different subgroups with negative log concentrations inhibiting movement in 50% of aggregates as follows: Class 1-nisoldipine (7.20); Class 2-verapamil (6.36), diltiazem (5.83); Class 3-lidoflazine (5.68), pimozide (6.25). 3. The effects of the dihydropyridine facilitators Bay K 8644 and CGP 28392 on aggregate beating were investigated by evaluating the interaction between calcium channel facilitators and antagonists from the three subgroups of calcium antagonists. Concentrations of antagonists that inhibited beating in 85% of aggregates were used. Both Bay K 8644 and CGP 28392 reversed nisoldipine-, diltiazem- or verapamil-induced inhibition of beating. 4. Bay K 8644 was approximately 10 times more potent than CGP 28392 in reversing nisoldipine-, diltiazem- or verapamil-induced inhibition of beating. 5. For each facilitator the concentrations causing 50% reversal of inhibition of aggregate beating against the three antagonists were similar. There was little evidence for differential modulation by verapamil or diltiazem of the action of the dihydropyridine facilitators. 6. Bay K 8644 did not reverse lidoflazine- or pimozide-induced inhibition of beating, indicating that these drugs may act at a site distinct from the dihydropyridine site on the calcium channel.
Patmore
L
L
Department of Pharmacology, Syntex Research Centre, Riccarton, Edinburgh.
Duncan
G P
GP
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D009206:Myocardium / Q000166:cytology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers