Send to

Choose Destination
See comment in PubMed Commons below
Neurology. 2000 Feb 22;54(4):937-42.

Functional consequences of chloride channel gene (CLCN1) mutations causing myotonia congenita.

Author information

Department of Neurology, University of Utah, Salt Lake City 84112-5331, USA.



To determine the functional consequences of missense mutations within the skeletal muscle chloride channel gene CLCN1 that cause myotonia congenita.


Myotonia congenita is a genetic muscle disease associated with abnormalities in the skeletal muscle voltage-gated chloride (ClC-1) channel. In order to understand the molecular basis of this inherited disease, it is important to determine the physiologic consequences of mutations found in patients affected by it.


The authors used a mammalian cell (human embryonic kidney 293) expression system and the whole-cell voltage-clamp technique to functionally express and physiologically characterize five CLCN1 mutations.


The I329T mutation shifted the voltage dependence of open probability of ClC-1 channels to the right by 192 mV, and the R338Q mutation shifted it to the right by 38 mV. In addition, the I329T ClC-1 channels deactivated to a lesser extent than normal at negative potentials. The V165G, F167L, and F413C ClC-1 channels also shifted the voltage dependence of open probability, but only by +14 to +20 mV.


The functional consequences of these mutations form the physiologic argument that these are disease-causing mutations and could lead to myotonia congenita by impairing the ability of the skeletal muscle voltage-gated chloride channels to maintain normal muscle excitability. Understanding of genetic and physiologic defects may ultimately lead to better diagnosis and treatment of patients with myotonia congenita.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center