Calcium induced reversible alterations in excitation-contraction coupling in verapamil treated rat myocardium

We studied the effects of a calcium channel blocking agent, verapamil (V) (2 to 10 micrograms/ml), in the presence of increasing external calcium on simultaneously recorded transmembrane electrophysiological properties and mechanical function of rat myocardium. Left ventricular papillary muscles from male Fischer 344 rats were studied electrically, by standard microelectrode techniques, and mechanically in an isolated tissue bath at 30 degrees C. Control (0 micrograms/ml V + 2.4 mM Ca2+) = C, action potential duration at 50% and 75% repolarization (D50ap and D75ap) recorded from papillary muscles were short (14.1 +/- 0.75 ms; 33.3 +/- 2.7 ms) compared with recordings from papillary muscles subjected to increasing doses of verapamil (2, 4, 6, 8, or 10 micrograms/ml) + 2.4 mM Ca2+ = V, (17.3 +/- 0.77 ms; 121.4 +/- 8.9 ms: 10 micrograms/ml) (P less than 0.001). Upon augmentation of external calcium [10 micrograms/ml Verapamil + augmented Ca2+ (4.8, 7.2, or 9.6 mM] = VCa, D50ap and D75ap decreased but still remained significantly longer than control D50ap and D75ap (15.1 +/- 0.77 ms; 110.1 +/- 7.9 ms). Developed tension (Td), time to peak developed tension (TPT), time to one-half relaxation (T1/2R) and resting tension (Tr) decreased as a function of verapamil concentration. Although TPT and T1/2R returned toward C values when external calcium was increased, Tr continued to decrease while Td increased above control levels. A significant correlation was found between measured parameters of contraction and transmembrane action potential for C and VCa muscles. However, in V muscles no significant correlation was observed between these same mechanical and electrical parameters.(ABSTRACT TRUNCATED AT 250 WORDS)