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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Expression and canalicular localization of two isoforms of the ClC-3 chloride channel from rat hepatocytes.

The molecular identities of functional chloride channels in hepatocytes are largely unknown. We examined the ClC-3 chloride channel in rat hepatocytes and found that mRNA for two different isoforms is present. A short form is identical to the previously reported sequence for rat ClC-3, and a long form contains a 176-bp insertion immediately upstream of the translation initiation site. This predicts a 58-amino acid NH(2) terminal insertion. Both long and short form mRNA was expressed in diverse tissues of the rat. Transient transfection of the long form in CHO-K1 cells resulted in currents with an I(-) > B(-) > Cl(-) selectivity sequence, outward rectification, and inactivation at positive voltages. Short form currents had identical ionic selectivity but displayed a more extreme outward rectification and showed no voltage-dependent inactivation. Immunofluorescence and immunoblots localized native ClC-3 preferentially but not exclusively to the canalicular membrane. We have therefore identified a new isoform of rat ClC-3 and shown that expression of both isoforms produces functional channels. In hepatocytes, ClC-3 is located in association with the canalicular membrane.[1]


  1. Expression and canalicular localization of two isoforms of the ClC-3 chloride channel from rat hepatocytes. Shimada, K., Li, X., Xu, G., Nowak, D.E., Showalter, L.A., Weinman, S.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
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