Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells.

Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells. Research Abstract Details 

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Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells. Abstract Text:

Man Zhang,Wen-Jie Shi,Xiao-Wei Fei,Ya-Rong Liu,Xi-Min Zeng,Yan-Ai Mei,

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K(+) current (I(A)) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 muM to 100 muM, mefenamic acid reversibly inhibited I(A) in a dose-dependent manner. However, mefenamic acid at a concentration of 1 muM significantly increased the amplitude of I(A) to 113+/-1.5% of the control. At more than 10 muM, mefenamic acid inhibited the amplitude of I(A) without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I(A), but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I(A) channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.

Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells. Publishing Authors By Initials

M Zhang,WJ Shi,XW Fei,YR Liu,XM Zeng,YA Mei,

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Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Toxicology and applied pharmacology

VOLUME: 226

Page Numbers: 225-35

Journal Abbreviation: Toxicol. Appl. Pharmacol.

ISSN: 0041-008X

DAY: 19

MONTH: 09

YEAR: 2007

Mefenamic acid bi-directionally modulates the transient outward K(+) current in rat cerebellar granule cells. Information

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LANGUAGE: eng

NlmUniqueID: 416575

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AFFILIATION: Institute of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, P.R. China.

Country: United States

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MEDLINETA: Toxicol Appl Pharmacol

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