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A more recent version of this article appeared on October 28, 2005
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M507706200v1
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Papers In Press, published online ahead of print August 29, 2005
J. Biol. Chem, 10.1074/jbc.M507706200
Submitted on July 15, 2005
Revised on August 26, 2005
Accepted on August 29, 2005

Identification and functional characterization of a voltage-gated chloride channel and its novel splice variant in taste bud cells

Liquan Huang, Jie Cao, Hong Wang, Lynn A. Vo, and Joseph G. Brand

Monell Chemical Senses Center, Philadelphia, PA 19104

Corresponding Author: LHUANG{at}monell.org

Taste bud cells are epithelial cells with neuronal properties. Voltage-dependent ion channels have been physiologically described in these cells. Here we report the molecular identification and functional characterization of a voltage-gated chloride channel ClC-4 and its novel splice variant ClC-4A from taste bud cells. ClC-4A skips an exon near its 5’-end, which incurs the loss of 60 amino acids at the amino terminus. In situ hybridization and immunohistochemistry localized these two channels´ transcripts and proteins to a subset of taste bud cells. Electrophysiological recordings of the heterologously expressed channels in Xenopus oocytes showed that ClC-4 and ClC-4A had the opposite sensitivity to pH, and unique ion selectivity. The chloride channel blockers niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) had slight or no inhibitory effect on the conductance of ClC-4, but both blockers inhibited ClC-4A, suggesting that ClC-4A is a candidate channel for an acid-induced NPPB-sensitive current. Furthermore, these two channels may play a role in bitter--, sweet-- and umami--mediated taste transmission by regulating transmitter uptake into synaptic vesicles.


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