AHEART May 47/5

Ferrier, Gregory R., Isabel M. Redondo, Cindy A. Mason, Cindy Mapplebeck, and Susan E. Howlett. Regulation of contraction and relaxation by membrane potential in cardiac ventricular myocytes. Am J Physiol Heart Circ Physiol 278: H1618–H1626, 2000.—Control of contraction and relaxation by membrane potential was investigated in voltageclamped guinea pig ventricular myocytes at 37°C. Depolarization initiated phasic contractions, followed by sustained contractions that relaxed with repolarization. Corresponding Ca21 transients were observed with fura 2. Sustained responses were ryanodine sensitive and exhibited sigmoidal activation and deactivation relations, with half-maximal voltages near 246 mV, which is characteristic of the voltagesensitive release mechanism (VSRM) for sarcoplasmic reticulum Ca21. Inactivation was not detected. Sustained responses were insensitive to inactivation or block of L-type Ca21 current (ICa-L). The voltage dependence of sustained responses was not affected by changes in intracellular or extracellular Na1 concentration. Furthermore, sustained responses were not inhibited by 2 mM Ni21. Thus it is improbable that ICa-L or Na1/Ca21 exchange generated these sustained responses. However, rapid application of 200 μM tetracaine, which blocks the VSRM, strongly inhibited sustained contractions. Our study indicates that the VSRM includes both a phasic inactivating and a sustained noninactivating component. The sustained component contributes both to initiation and relaxation of contraction.