PUB - Publikationen an der Universität Bielefeld

1. In mature mammalian muscle, the muscular chloride channel CIC-1 contributes about 75% of the sarcolemmal resting conductance (G(m)). In mice carrying two defective alleles of the corresponding Clc1 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 is 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.