Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na+ currents, NaV1.6, in murine vas deferens myocytes

Hai Lei Zhu, Richard D. Wassall, Maki Takai, Hidetaka Morinaga, Masatoshi Nomura, Thomas C. Cunnane, Noriyoshi Teramoto

Research output: Contribution to journalArticle

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Abstract

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 (INa) in vas deferens myocytes dispersed from BALB/c mice, homozygous mice with a null allele of NaV1.6 (NaV1.6-/-) and wild-type mice (NaV1.6+/+) 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 INa: INa was enhanced by veratridine (1-10 mM), while higher concentrations (≥30 μM) inhibited INa. 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 INa, veratridine enhanced a non-inactivating component of INa. Veratridine caused no detectable contractions in vas deferens from NaV1.6-/-mice, although in tissues from NaV1.6+/+ mice, veratridine (≥3 μM) induced TTX-sensitive contractions. Similarly, no detectable inward currents were evoked by veratridine in NaV1.6-/-vas deferens myocytes, while veratridine elicited both the sustained and tail currents in cells taken from NaV1.6+/+ mice. Conclusions and implications: These results suggest that veratridine possesses a dual action on INa and that the veratridineinduced activation of contraction is induced by the activation of NaV1.6 channels.

Original languageEnglish
Pages (from-to)1483-1493
Number of pages11
JournalBritish Journal of Pharmacology
Volume157
Issue number8
DOIs
Publication statusPublished - Oct 29 2009

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Veratridine
Vas Deferens
Tetrodotoxin
Muscle Cells
Tail
Liliaceae
Patch-Clamp Techniques
Alkaloids

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na+ currents, NaV1.6, in murine vas deferens myocytes. / Zhu, Hai Lei; Wassall, Richard D.; Takai, Maki; Morinaga, Hidetaka; Nomura, Masatoshi; Cunnane, Thomas C.; Teramoto, Noriyoshi.

In: British Journal of Pharmacology, Vol. 157, No. 8, 29.10.2009, p. 1483-1493.

Research output: Contribution to journalArticle

Zhu, Hai Lei ; Wassall, Richard D. ; Takai, Maki ; Morinaga, Hidetaka ; Nomura, Masatoshi ; Cunnane, Thomas C. ; Teramoto, Noriyoshi. / Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na+ currents, NaV1.6, in murine vas deferens myocytes. In: British Journal of Pharmacology. 2009 ; Vol. 157, No. 8. pp. 1483-1493.
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abstract = "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 (INa) in vas deferens myocytes dispersed from BALB/c mice, homozygous mice with a null allele of NaV1.6 (NaV1.6-/-) and wild-type mice (NaV1.6+/+) 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 INa: INa was enhanced by veratridine (1-10 mM), while higher concentrations (≥30 μM) inhibited INa. 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 INa, veratridine enhanced a non-inactivating component of INa. Veratridine caused no detectable contractions in vas deferens from NaV1.6-/-mice, although in tissues from NaV1.6+/+ mice, veratridine (≥3 μM) induced TTX-sensitive contractions. Similarly, no detectable inward currents were evoked by veratridine in NaV1.6-/-vas deferens myocytes, while veratridine elicited both the sustained and tail currents in cells taken from NaV1.6+/+ mice. Conclusions and implications: These results suggest that veratridine possesses a dual action on INa and that the veratridineinduced activation of contraction is induced by the activation of NaV1.6 channels.",
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AU - Zhu, Hai Lei

AU - Wassall, Richard D.

AU - Takai, Maki

AU - Morinaga, Hidetaka

AU - Nomura, Masatoshi

AU - Cunnane, Thomas C.

AU - Teramoto, Noriyoshi

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