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Chloride conductance in mouse muscle is subject to post‐transcriptional compensation of the functional Cl − channel 1 gene dosage
Author(s) -
Chen Meifang,
Niggeweg Ricarda,
Iaizzo Paul A.,
LehmannHorn Frank,
Jockusch Harald
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.075bf.x
Subject(s) - chloride channel , myotonia , heterozygote advantage , wild type , allele , conductance , endocrinology , medicine , chemistry , gene , skeletal muscle , microbiology and biotechnology , biology , biochemistry , myotonic dystrophy , mutant , mathematics , combinatorics
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.