Isolated rat cardiac myocytes as an experimental model to study calcium overload: the effect of calcium-entry blockers.
Calcium overload and the effect of a series of calcium-entry blockers were studied in isolated adult cardiac myocytes from the rat challenged with veratrine. The isolation procedure resulted in a high yield of individual rod shaped, calcium tolerant myocytes. After incubation with veratrine, an alkaloid which induces both sodium and calcium influx, 93% of the myocytes became calcium intolerant: the quiescent rod shaped cells vigorously contracted after 30 sec of contact with veratrine and contracture (round cells) ensued within 1 min. Exposure for 30 min to various doses of calcium-entry blockers prior to veratrine addition resulted in the prevention of contracture, the degree of protection depending on the type and the concentration of calcium-entry blocker. Among the different calcium-entry blockers tested, the diarylalkylpiperazines lidoflazine, cinnarizine and flunarizine were protective from the 10(-7) M concentration onwards. Nicardipine was protective at the 10(-6) M and 10(-5) M concentrations, verapamil at 10(-5)M only while other blockers of the "slow channel" type (diltiazem and nifedipine) were not protective in the concentration range tested. This study shows that isolated myocytes represent a valid model for pharmacological investigations. The results with the calcium-entry blockers stress the heterogeneity of the different series of calcium-entry blockers.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002936:Cinnarizine / Q000031:analogs & derivatives / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D005444:Flunarizine; D006321:Heart / Q000187:drug effects; D008013:Lidoflazine / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002936:Cinnarizine; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D014702:Veratrine; D009543:Nifedipine; D008013:Lidoflazine; D005444:Flunarizine; D002118:Calcium