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In heart muscle, strong evidence shows that excitation-contraction coupling involves Ca-induced Ca-release. However, under some conditions, single heart cells show Ca release and contraction which is not correlated with Ca entry via the Ca channel, suggesting a second Ca-independent release mechanism. Similar observations were made in early, pioneering studies using voltage-clamped multi-cellular preparations. We review the influence that experimental preparations and conditions have had on excitation-contraction coupling theory over the last 20 years.

Coming full circle Membrane potential, sarcolemmal calcium influx and excitation–contraction coupling in heart muscle