Excitation Contraction Coupling in Cardiac Muscle : Is there a Purely Voltage-dependent Component?

It is well established that excitation contraction (EC) coupling in cardiac myocytes is mediated by the entry of calcium ions (Ca²⁺) from the bathing medium into the cell cytoplasm (Fabiato, 1985), which then triggers calcium-induced calcium release (CICR) from the sarcoplasmic reticulum (SR). More recently, it was proposed that a second, quite separate, EC-coupling process, mediated by an effect of membrane potential per se on SR Ca²⁺ release, also operates in cardiac myocytes (Ferrier and Howlett, 1995; Hobai et al., 1997; Howlett and Ferrier, 1997; Howlett et al., 1998, 1999; Ferrier et al., 1998, 2000; Mason and Ferrier, 1999; Zhu and Ferrier, 2000; for review see Ferrier and Howlett, 2001). Although a substantial body of diverse experimental observations has been reported in support of this voltage-sensitive release mechanism (VSRM;...