Excitation-contraction coupling in cardiac myocytes occurs by Ca-induced Ca release, where L-type Ca current evokes a larger sarcoplasmic reticulum (SR) Ca release. The Ca-induced Ca release amplification factor or gain (SR Ca release/ICa) is usually assessed by the Vm dependence of current and Ca transients. Gain rises at negative Vm, as does single channel ICa (iCa), which has led to the suggestion that the increases of iCa amplitude enhances gain at more negative Vm. However, ICa=NPo×iCa (where NPo is the number of open channels), and NPo and iCa both depend on Vm. To assess how iCa and NPo separately influence Ca-induced Ca release, we measured ICa and junctional SR Ca release in voltage-clamped rat ventricular myocytes using "Ca spikes" (confocal microscopy). To vary iCa alone, we changed [Ca]o rapidly at constant test Vm (0 mV) or abruptly repolarized from +120 mV to different Vm (at constant [Ca]o). To vary NPo alone, we altered Ca channel availability by varying holding Vm (at constant test Vm). Reducing either iCa or NPo alone increased excitation-contraction coupling gain. Thus, increasing iCa does not increase gain at progressively negative test Vm. Such enhanced gain depends on lower NPo and reduced redundant Ca channel openings (per junction) and a consequently smaller denominator in the gain equation. Furthermore, modest iCa (at Vm=0 mV) may still effectively trigger SR Ca release, whereas at positive Vm (and smaller iCa), high and well-synchronized channel openings are required for efficient excitation-contraction coupling. At very positive Vm, reduced iCa must explain reduced SR Ca release.
- Calcium-induced calcium release
- Excitation-contraction coupling
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine