Key result
Disease-associated mutations in voltage-gated sodium channels alter channel gating to produce exaggerated resurgent sodium currents, potentially promoting repetitive neuronal firing and myotonia.
Enhanced resurgent sodium current may be a common pathophysiological mechanism across various neuronal and muscle channelopathies, including cardiac arrhythmias.
Voltage-dependent sodium channels are the central players in the excitability of neurons, cardiac muscle, and skeletal muscle. Hundreds of mutations in sodium channels have been associated with human disease, particularly genetic forms of epilepsy, arrhythmias, myotonia, and periodic paralysis. In this issue of the JCI, Jarecki and colleagues present evidence suggesting that many such mutations alter the gating of sodium channels to produce resurgent sodium current, an unusual form of gating in which sodium channels reopen following an action potential, thus promoting the firing of another action potential (see the related article beginning on page 369). The results of this study suggest a widespread pathophysiological role for this mechanism, previously described to occur normally in only a few types of neurons.
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Cannon et al. (2010) conducted an editorial in Channelopathies. Voltage-gated sodium channel mutations vs. Wild-type sodium channels was evaluated. Disease-associated mutations in voltage-gated sodium channels alter channel gating to produce exaggerated resurgent sodium currents, potentially promoting repetitive neuronal firing and myotonia.
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