Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca(2+) channel and the sarcoplasmic reticulum Ca(2+) release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca(2+)-bound and Ca(2+)-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.