Effects of Calcium Channel Antagonists on Ca2+Transients in Rat and Canine Cardiomyocytes

• Published in: Journal of molecular and cellular cardiology 1997-03, Vol.29 (3), p.1037-1043
• Main Authors: Hensley, James, Billman, George E., Johnson, J.David, Hohl, Charlene M., Altschuld, Ruth A.
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Bay K 8644; Biological Transport; Calcium - metabolism; Calcium Channel Agonists - pharmacology; Calcium channel antagonists; Calcium Channel Blockers - pharmacology; Canine myocytes; Cardiotonic Agents - pharmacology; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Felodipine; Female; Free calcium transients; Heart Ventricles - drug effects; Male; Mibefradil; Myocardium - cytology; Myocardium - metabolism; Nifedipine; Rat myocytes; Rats; Rats, Sprague-Dawley; Species Specificity; Verapamil
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1996.0348

First-generation Ca2+channel antagonists depress myocardial contractility, but many of the newer Ca2+channel blockers have a high degree of “vascular selectivity”. This study compares the effects of the Ca2+antagonists felodipine, amlodipine, mibefradil, verapamil and nifedipine, and the Ca2+channel agonist, (S)(−)-Bay K-8644 on Ca2+transient amplitudes in fura-2/AM-loaded rat and canine ventricular cardiomyocytes. At 10−11and 10−10m, felodipine increased [Ca2+]itransient amplitudes by 10–25% in field-stimulated fura-2-loaded cells from both species while at 10−6mit depressed [Ca2+]itransients by 80%. Mibefradil increased [Ca2+]itransient amplitudes by 16% at 10−11and 10−10mand decreased the transients by 25% at 10−6m. The calcium channel agonist, (S)(−)-Bay K-8644 increased [Ca2+]itransient amplitudes at 10−10–10−6m(maximally 37% at 10−7m) but depressed [Ca2+]itransients by 10% at 10−5M. Nifedipine was inhibitory at all concentrations tested (10−11–10−6m) in canine myocytes, but in rat cells, 10−10mnifedipine increased [Ca2+]itransient amplitudes by 37%. All concentrations of verapamil and amlodipine (10−11–10−6m) depressed [Ca2+]itransients in both rat and canine myocytes. We conclude that: (1) felodipine and mibefradil may be positive rather than negative inotropes at low concentrations, which are therapeutically relevant; and (2) low concentrations of nifedipine may have a positive inotropic effect in the rat but not the dog heart.