Actions of kurtoxin on tetrodotoxin-sensitive voltage-gated Na+ currents, NaV1.6, in murine vas deferens myocytes.
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.
Zhu
Hai-Lei
HL
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka, 812-8582, Japan.
Wassall
Richard D
RD
Cunnane
Thomas C
TC
Teramoto
Noriyoshi
N
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018408:Patch-Clamp Techniques; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000096:biosynthesis; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D049990:Membrane Transport Modulators; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D012604:Scorpion Venoms; D015222:Sodium Channels; C118444:kurtoxin; D013779:Tetrodotoxin