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

J Physiol. 1997 Oct 1;504 ( Pt 1)(Pt 1):75-81. doi: 10.1111/j.1469-7793.1997.075bf.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chloride Channels / genetics*
  • Chloride Channels / metabolism
  • Chloride Channels / physiology*
  • Gene Dosage*
  • Genes
  • Genotype
  • Mice
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Mutation
  • Myotonia / genetics
  • Myotonia / metabolism
  • Protein Processing, Post-Translational / genetics
  • Protein Processing, Post-Translational / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Sarcolemma / metabolism

Substances

  • Chloride Channels
  • RNA, Messenger