Chloride conductance in mouse muscle is subject to post-transcriptional compensation of the functional Cl- channel 1 gene dosage

Mei Fang Chen, Ricarda Niggeweg, Paul A. Iaizzo, Frank Lehmann-Horn, Harald Jockusch

Research output: Contribution to journalArticlepeer-review

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Abstract

1. In mature mammalian muscle, the muscular chloride channel C1C-1 contributes about 75% of the sarcolemmal resting conductance (G(m)) In mice carrying two defective alleles of the corresponding Clc1 gene, chloride conductance (G(Cl)) is reduced to less than 10% of that of wild-type, and this causes hyperexcitability, the salient feature of the disease myotonia. Potassium conductance (G(K)) values in myotonic mouse muscle fibres are lowered by about 60% compared with wild-type. 2. The defective Clc(adr) allele causes loss of the 4.5 kb ClC-1 mRNA. Mice heterozygous for the defective Clc1(adr) allele contain about 50% functional mRNA in their muscles compared with homozygous wild-type mice. 3. Despite a halved functional gene dosage, heterozygous muscles display an average G(Cl) which is not significantly different from that of homozygous wild-type animals. The G(K) values in heterozygotes are also indistinguishable from homozygous wild-type animals. 4. These results indicate that a regulatory mechanism acting at the post-transcriptional level limits the density of ClC-1. channels. G(K) is probably indirectly regulated by muscle activity.

Original languageEnglish (US)
Pages (from-to)75-81
Number of pages7
JournalJournal of Physiology
Volume504
Issue number1
DOIs
StatePublished - Oct 1 1997

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