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Actions of kurtoxin on tetrodotoxin-sensitive voltage-gated Na+ currents, NaV1.6, in murine vas deferens myocytes
Hai-Lei Zhu1, Richard D Wassall, Thomas C Cunnane
1Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka, 812-8582, Japan.
Abstract:
Kurtoxin is described as a selective inhibitor of Ca(V)3.1. Using patch-clamp techniques, the modulatory effects of kurtoxin on tetrodotoxin-sensitive voltage-gated Na(+) currents (I(Na)) recorded from mouse vas deferens myocytes were investigated. Kurtoxin increased the peak amplitude of I(Na) between -40 and -30 mV, whilst inhibited the peak amplitude at more positive potentials than -10 mV, thereby demonstrating a dual action on the peak amplitude of I(Na). The time to reach the peak amplitude of I(Na) became significantly longer in the presence of kurtoxin in comparison with that of the controls. Kurtoxin also slowed the deactivation of I(Na) at more positive membrane potentials than -30 mV. Kurtoxin enhanced the total amount of electrical charge of I(Na) in a concentration-dependent manner. These results suggest that kurtoxin is a modulator of Na(V)1.6 in native freshly dispersed smooth muscle cells from mouse vas deferens as well as its action on Ca(V)3.1.
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