CONTRIBUTION OF A VOLTAGE-SENSITIVE CALCIUM-RELEASE MECHANISM TO CONTRACTION IN CARDIAC VENTRICULAR MYOCYTES

The contribution of a voltage-sensitive release mechanism (VSRM) for s arcoplasmic reticulum (SR) Ca2+ to contraction was investigated in vol tage-clamped ventricular myocytes at 37 degrees C. Na+ current was blo cked with lidocaine. The VSRM exhibited steady-state inactivation (hal f-inactivation voltage: -47.6 mV; slope factor: 4.37 mV). When the VSR M was inactivated, contraction-voltage relationships were proportional to L-type Ca2+ current (ICa-L). When the VSRM was available, the rela tionship was sigmoidal, with contractions independent of voltage posit ive to -20 mV. VSRM and ICa-L contractions could be separated by activ ation-inactivation properties. VSRM contractions were extremely sensit ive to ryanodine, thapsigargin, and conditioning protocols to reduce S R Ca2+ load. ICa-L contractions were less sensitive. When both VSRM an d ICa-L were available, sigmoidal contraction-voltage relationships be came bell-shaped with protocols to reduce SR Ca2+ load. Myocytes demon strated restitution of contraction that was slower than restitution of ICa-L. Restitution was a property of the VSRM. Thus activation and re covery of the VSRM are important in coupling cardiac contraction to me mbrane potential, SR Ca2+ load, and activation interval.