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

Abstract A mechanism underlying the increase in rat heart contractility modulated by BmK I, an α-like scorpion neurotoxin, was investigated using whole-cell patch-clamp and fluorescence digital imaging techniques. Results showed that (a) L-type Ca 2+ 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 Ca 2+ concentration could be augmented in the presence of BmK I; ( p 2+ concentration induced by BmK I was inhibited completely by 5 mM NiCl 2 ( p + –Ca 2+ exchanger; (e) The spontaneous Ca 2+ release induced by 10 mM caffeine from sarcoplasmic reticulum could not be modulated by 500 nM BmK I in the absence of external Ca 2+ . These results indicate that cardiac voltage-gated Na + channels are also targets of BmK I. Na + accumulation through Na + channels can trigger sarcoplasmic reticulum Ca 2+ release in rat cardiac myocytes via reverse-mode Na + –Ca 2+ exchanger. Furthermore, Ca 2+ release from sarcoplasmic reticulum induced by BmK I most likely involves a Ca 2+ -induced release mechanism.