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 (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.
Chen
M F
MF
Developmental Biology Unit, University of Bielefeld, Germany.
Niggeweg
R
R
Iaizzo
P A
PA
Lehmann-Horn
F
F
Jockusch
H
H
D000483:Alleles; D000818:Animals; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018628:Gene Dosage; D005796:Genes; D005838:Genotype; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009222:Myotonia / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012508:Sarcolemma / Q000378:metabolism
D018118:Chloride Channels; D012333:RNA, Messenger