The role of voltage-gated Na+ channels in excitation-contraction coupling of rat heart determined by BmK I, an alpha-like scorpion neurotoxin.

A mechanism underlying the increase in rat heart contractility modulated by BmK I, an alpha-like scorpion neurotoxin, was investigated using whole-cell patch-clamp and fluorescence digital imaging techniques. Results showed that (a) L-type Ca2+ current could not be modified by 500 nM BmK I; (b) The inactivation process of Na+ current was significantly delayed with no change of its amplitude; (c) The overall intracellular Na+ and Ca2+ concentration could be augmented in the presence of BmK I; (p<0.05); (d) The increase of free intracellular Ca2+ concentration induced by BmK I was inhibited completely by 5 mM NiCl2 (p<0.05), an inhibitor of Na+-Ca2+ exchanger; (e) The spontaneous Ca2+ release induced by 10 mM caffeine from sarcoplasmic reticulum could not be modulated by 500 nM BmK I in the absence of external Ca2+. These results indicate that cardiac voltage-gated Na+ channels are also targets of BmK I. Na+ accumulation through Na+ channels can trigger sarcoplasmic reticulum Ca2+ release in rat cardiac myocytes via reverse-mode Na+-Ca2+ exchanger. Furthermore, Ca2+ release from sarcoplasmic reticulum induced by BmK I most likely involves a Ca2+-induced release mechanism.