Channelpedia

PubMed 16770776


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC1 , ClvC4



Title: Acetazolamide acts directly on the human skeletal muscle chloride channel.

Authors: Hiroto Eguchi, Akira Tsujino, Muneshige Kaibara, Hideki Hayashi, Susumu Shirabe, Kohtaro Taniyama, Katsumi Eguchi

Journal, date & volume: Muscle Nerve, 2006 Sep , 34, 292-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16770776


Abstract
Acetazolamide, a carbonic anhydrase inhibitor, is used empirically in neuromuscular diseases with episodic ataxia, weakness, and myotonia, although not all of the mechanisms responsible for its therapeutic effects are understood. To elucidate whether acetazolamide acts directly on the human skeletal muscle voltage-gated chloride channel (ClC-1), which is associated with myotonia, we evaluated the effects of acetazolamide on ClC-1 expressed in cultured mammalian cells, using whole-cell recording. Acetazolamide significantly shifted the voltage dependency of the open probability (P(o)) toward negative potentials in a dose-dependent manner, resulting in an increase of chloride conductance at voltages near the resting membrane potential. This effect was attenuated when using a pipette solution containing 30 mmol/L Hepes. These results suggest that acetazolamide can influence the voltage-dependent opening gate of ClC-1 through a mechanism related to intracellular acidification by inhibiting carbonic anhydrase, and that the therapeutic effects of acetazolamide in neuromuscular diseases may be mediated by activation of ClC-1.