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XB-ART-13449
J Gen Physiol 1999 Mar 01;1133:457-68.
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The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia.

Saviane C , Conti F , Pusch M .


Abstract
Single-channel recordings of the currents mediated by the muscle Cl- channel, ClC-1, expressed in Xenopus oocytes, provide the first direct evidence that this channel has two equidistant open conductance levels like the Torpedo ClC-0 prototype. As for the case of ClC-0, the probabilities and dwell times of the closed and conducting states are consistent with the presence of two independently gated pathways with approximately 1.2 pS conductance enabled in parallel via a common gate. However, the voltage dependence of the common gate is different and the kinetics are much faster than for ClC-0. Estimates of single-channel parameters from the analysis of macroscopic current fluctuations agree with those from single-channel recordings. Fluctuation analysis was used to characterize changes in the apparent double-gate behavior of the ClC-1 mutations I290M and I556N causing, respectively, a dominant and a recessive form of myotonia. We find that both mutations reduce about equally the open probability of single protopores and that mutation I290M yields a stronger reduction of the common gate open probability than mutation I556N. Our results suggest that the mammalian ClC-homologues have the same structure and mechanism proposed for the Torpedo channel ClC-0. Differential effects on the two gates that appear to modulate the activation of ClC-1 channels may be important determinants for the different patterns of inheritance of dominant and recessive ClC-1 mutations.

PubMed ID: 10051520
PMC ID: PMC2222904

Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: clcn1
GO keywords: voltage-gated chloride channel activity

Disease Ontology terms: myotonia congenita
OMIMs: MYOTONIA CONGENITA, AUTOSOMAL DOMINANT [+]

Article Images: [+] show captions
References [+] :
Chen, Nonequilibrium gating and voltage dependence of the ClC-0 Cl- channel. 1996, Pubmed