The contribution of a voltage-sensitive release mechanism (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 ( I Ca-L). When the VSRM was available, the relationship was sigmoidal, with contractions independent of voltage positive to −20 mV. VSRM and I Ca-Lcontractions could be separated by activation-inactivation properties. VSRM contractions were extremely sensitive to ryanodine, thapsigargin, and conditioning protocols to reduce SR Ca2+ load. I Ca-Lcontractions were less sensitive. When both VSRM and I Ca-L were available, sigmoidal contraction-voltage relationships became bell-shaped with protocols to reduce SR Ca2+ load. Myocytes demonstrated restitution of contraction that was slower than restitution of I 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.

It is well established that initiation of contraction in cardiac muscle is triggered by a rise in intracellular free Ca¥. Only two sources are believed to contribute significantly to this increase in Ca¥: (1) influx of Ca¥ through the sarcolemma, primarily through voltage-gated L-type Ca¥ channels and sometimes by reverse Na¤-Ca¥ exchange (Na¤-Ca¥ex), and (2) release of internal stores of Ca¥ from the sarcoplasmic reticulum (SR) by way of SR release channels, also known as ryanodine receptors. SR Ca¥ release triggered by depolarization of the sarcolemma can occur via a mechanism described by Fabiato (1985) called Ca¥-induced Ca¥ release (CICR). With this mechanism, a small amount of Ca¥ entering the cell as L-type Ca¥ current (ICa,L) or by way of reverse Na¤-Ca¥ex can bind to an activation site on the SR

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Preservation of VSRM contractions during block of I(Ca-L), may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function.

The objective of this study was to identify cellular electrophysiological mechanisms by which ischemic preconditioning decreases arrhythmias in an isolated ventricular tissue model of ischemia and reperfusion. Electrical activity was recorded with microelectrodes from endocardium and epicardium of paced guinea pig right ventricular free walls. Control preparations were exposed for 15 min to Tyrode solution modified to simulate selected ischemic conditions and then were reperfused for 30 min with normal solution. Preconditioned tissues were exposed to a 2- or 5-min period of simulated ischemia before this same protocol. Neither preconditioning protocol affected incidence of ventricular tachycardia (VT) in ischemia; however, the 5-min protocol significantly decreased premature beats (PVB) and transmural conduction block. Preconditioning for 5 min, but not 2 min, significantly decreased reperfusion-induced VT and PVB. Ischemic preconditioning did not change effects of ischemia or reperfusion on action potential duration, effective refractory period, or endocardial conduction time. However, preconditioning markedly attenuated depression of transmural conduction by ischemia and early reperfusion and thereby prevented conduction delays necessary for transmural reentry.