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

1 In mature mammalian muscle, the muscular chloride channel ClC‐1 contributes about 75% of the sarcolemmal resting conductance ( G m ). In mice carrying two defective alleles of the corresponding Clc 1 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.