Document Detail


Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na currents, Na1.6, in murine vas deferens myocytes.
MedLine Citation:
PMID:  19552689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: The effects of veratridine, an alkaloid found in Liliaceae plants, on tetrodotoxin (TTX)-sensitive voltage-gated Na(+) channels were investigated in mouse vas deferens.
EXPERIMENTAL APPROACH: Effects of veratridine on TTX-sensitive Na(+) currents (I(Na)) in vas deferens myocytes dispersed from BALB/c mice, homozygous mice with a null allele of Na(V)1.6 (Na(V)1.6(-/-)) and wild-type mice (Na(V)1.6(+/+)) were studied using patch-clamp techniques. Tension measurements were also performed to compare the effects of veratridine on phasic contractions in intact tissues.
KEY RESULTS: In whole-cell configuration, veratridine had a concentration-dependent dual action on the peak amplitude of I(Na): I(Na) was enhanced by veratridine (1-10 microM), while higher concentrations (> or =30 microM) inhibited I(Na). Additionally, two membrane current components were evoked by veratridine, namely a sustained inward current during the duration of the depolarizing rectangular pulse and a tail current at the repolarization. Although veratridine caused little shift of the voltage dependence of the steady-state inactivation curve and the activation curve for I(Na), veratridine enhanced a non-inactivating component of I(Na). Veratridine caused no detectable contractions in vas deferens from Na(V)1.6(-/-) mice, although in tissues from Na(V)1.6(+/+) mice, veratridine (> or =3 microM) induced TTX-sensitive contractions. Similarly, no detectable inward currents were evoked by veratridine in Na(V)1.6(-/-) vas deferens myocytes, while veratridine elicited both the sustained and tail currents in cells taken from Na(V)1.6(+/+) mice.
CONCLUSIONS AND IMPLICATIONS: These results suggest that veratridine possesses a dual action on I(Na) and that the veratridine-induced activation of contraction is induced by the activation of Na(V)1.6 channels.
Authors:
Hai-Lei Zhu; Richard D Wassall; Maki Takai; Hidetaka Morinaga; Masatoshi Nomura; Thomas C Cunnane; Noriyoshi Teramoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-22
Journal Detail:
Title:  British journal of pharmacology     Volume:  157     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-17     Completed Date:  2010-01-12     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1483-93     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Ion Channel Gating
Male
Membrane Potentials / drug effects
Mice
Mice, Inbred BALB C
Muscle Contraction
Myocytes, Smooth Muscle / drug effects*,  physiology
NAV1.6 Voltage-Gated Sodium Channel
Nerve Tissue Proteins / agonists*,  physiology
Patch-Clamp Techniques
Sodium Channel Agonists*
Sodium Channels / physiology
Tetrodotoxin / pharmacology
Vas Deferens / drug effects*,  physiology
Veratridine / pharmacology*
Chemical
Reg. No./Substance:
0/NAV1.6 Voltage-Gated Sodium Channel; 0/Nerve Tissue Proteins; 0/Scn8a protein, mouse; 0/Sodium Channel Agonists; 0/Sodium Channels; 4368-28-9/Tetrodotoxin; 71-62-5/Veratridine
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