Myotonia levior

Jong, J. G. Y. de

doi:10.1007/978-3-642-92920-5_33

Cited by 2 publications

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“…Following the linkage of Thomsen (dominant) and Becker (recessive) myotonia to CLCN1 , many disease‐causing mutations were identified and their properties investigated in heterologous expression systems, providing important insights into channel structure and function. Early clinical descriptions identified a discrete subgroup of patients with dominantly inherited but phenotypically mild disease, a condition termed myotonia levior (DeJong, 1966). In two of these patients, an arginine‐for‐glutamine substitution at position 552 of the CLCN1 gene (Q552R) was identified (Lehmann‐Horn et al 1995).…”

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A novel alteration of muscle chloride channel gating in myotonia levior

Ryan

Rüdel

Kuchenbecker

et al. 2002

The Journal of Physiology

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Mutations in the voltage-dependent skeletal muscle chloride channel, ClC-1, result in dominant or recessive myotonia congenita. The Q552R mutation causes a variant of dominant myotonia with a milder phenotype, myotonia levior. To characterise the functional properties of this mutation, homodimeric mutant and heterodimeric wild-type (WT) mutant channels were expressed in tsA201 cells and studied using the whole-cell recording technique. Q552R ClC-1 mutants formed functional channels with normal ion conduction but altered gating properties. Mutant channels were activated by membrane depolarisation, with a voltage dependence of activation that was shifted by more than +90 mV compared to WT channels. Q552R channels were also activated by hyperpolarisation, and this process was dependent upon the intracellular chloride concentration ([Cl _ ] i ). Together, these alterations resulted in a substantial reduction in the open probability at _85 mV at a physiological [Cl _ ] i . Heterodimeric WT-Q552R channels did not exhibit hyperpolarisation-activated gating transitions. As was the case for WT channels, activation occurred upon depolarisation, but the activation curve was shifted by 28 mV to more positive potentials. The functional properties of heterodimeric channels suggest a weakly dominant effect, a finding that correlates with the inheritance pattern and symptom profile of myotonia levior.

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confidence: 99%