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Science 312 (5773): 589-592

Copyright © 2006 by the American Association for the Advancement of Science

A Voltage Sensor-Domain Protein Is a Voltage-Gated Proton Channel

Mari Sasaki,1,2,3 Masahiro Takagi,1,3 Yasushi Okamura1,2,3,4*

Abstract: Voltage-gated proton channels have been widely observed but have not been identified at a molecular level. Here we report that a four-transmembrane protein similar to the voltage-sensor domain of voltage-gated ion channels is a voltage-gated proton channel. Cells overexpressing this protein showed depolarization-induced outward currents accompanied by tail currents. Current reversal occured at equilibrium potentials for protons. The currents exhibited pH-dependent gating and zinc ion sensitivity, two features which are characteristic of voltage-gated proton channels. Responses of voltage dependence to sequence changes suggest that mouse voltage-sensor domain–only protein is itself a channel, rather than a regulator of another channel protein.

1 Section of Developmental Neurophysiology, Okazaki Institute for Integrative Bioscience, Higashiyama 5-1, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.
2 The Graduate University for Advanced Studies, Higashiyama 5-1, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.
3 National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.
4 Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, Higashi 1-1-1, Tsukuba, Ibaraki 305-8566, Japan.

Note added in proof: D. Clapham's laboratory reports similar properties of a human ortholog, Hv1 (22).

* To whom correspondence should be addressed. E-mail: yokamura{at}

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PNAS 104, 18270-18275
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Development and Validation of Endogenous Reference Genes for Expression Profiling of Medaka (Oryzias latipes) Exposed to Endocrine Disrupting Chemicals by Quantitative Real-Time RT-PCR.
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2006: Signaling Breakthroughs of the Year.
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Sci. STKE 2007, eg1
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PNAS 103, 17548-17553
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J. Gen. Physiol. 127, 659-672
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Biophysics. Lonely voltage sensor seeks protons for permeation..
C. Miller (2006)
Science 312, 534-535
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