Contribution of a volt age-sensitive calcium release mechanism to contraction in cardiac ventricular myocytes

The contribution of a voltage-sensitive release mecha-nism (VSRM) for sarcoplasmic reticulum (SR) Ca²⁺ to contraction was investigated in voltage-clamped ventricular myocytes at 37°C. Na⁺ current was blocked with lidocaine. The VSRM exhibited steady-state inactivation (half-inactivation voltage: -47.6 mV; slope factor: 4.37 mV). When the VSRM was inactivated, contraction-voltage relationships were proportional to L-type Ca²⁺ current (/Ca-L)- When the VSRM was available, the relationship was sigmoidal, with contractions independent of voltage positive to -20 mV. VSRM and /ca-L contractions could be separated by activation-inactivation properties. VSRM contractions were extremely sensitive to ryanodine, thapsigargin, and conditioning protocols to reduce SR Ca²⁺ load. /ca-L contractions were less sensitive. When both VSRM and /ca.L were available, sigmoidal contractionvoltage relationships became bell-shaped with protocols to reduce SR Ca²⁺ load. Myocytes demonstrated restitution of contraction that was slower than restitution of /ca-L- Restitution was a property of the VSRM. Thus activation and recovery of the VSRM are important in coupling cardiac contraction to membrane potential, SR Ca²⁺ load, and activation interval.