Referenced in: none

Automatically associated channels: ClC1 , ClC4 , Kv2.1

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

Authors: M F Chen, R Niggeweg, P A Iaizzo, F Lehmann-Horn, H Jockusch

Journal, date & volume: J. Physiol. (Lond.), 1997 Oct 1 , 504 ( Pt 1), 75-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9350619

Abstract
1. In mature mammalian muscle, the muscular chloride channel ClC-1 contributes about 75% of the sarcolemmal resting conductance (Gm). In mice carrying two defective alleles of the corresponding Clc1 gene, chloride conductance (GCl) is reduced to less than 10% of that of wild-type, and this causes hyperexcitability, the salient feature of the disease myotonia. Potassium conductance (GK) values in myotonic mouse muscle fibres are lowered by about 60% compared with wild-type. 2. The defective Clcadr allele causes loss of the 4.5 kb ClC-1 mRNA. Mice heterozygous for the defective Clc1adr 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 GCl which is not significantly different from that of homozygous wild-type animals. The GK 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. GK is probably indirectly regulated by muscle activity.