| Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na currents, Na1.6, in murine vas deferens myocytes. | |
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MedLine Citation:
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PMID: 19552689 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hai-Lei Zhu; Richard D Wassall; Maki Takai; Hidetaka Morinaga; Masatoshi Nomura; Thomas C Cunnane; Noriyoshi Teramoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-22 |
Journal Detail:
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Title: British journal of pharmacology Volume: 157 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-17 Completed Date: 2010-01-12 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1483-93 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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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 Nerve Tissue Proteins / agonists*, physiology Patch-Clamp Techniques Sodium Channels / agonists*, physiology Tetrodotoxin / pharmacology Vas Deferens / drug effects*, physiology Veratridine / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Nerve Tissue Proteins; 0/Scn8a protein, mouse; 0/Sodium Channels; 4368-28-9/Tetrodotoxin; 71-62-5/Veratridine |
| Comments/Corrections | |
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