Sodium channel gating: no margin for error.

Voltage-gated Na(+) channels are the workhorses of spike generation and propagation in excitable cells. Mutations in Na(+) channel genes have been identified in disorders causing episodic dysfunction of heart, skeletal muscle, and brain. Lossin and colleagues from Al George's lab report in this issue of Neuron that three missense mutations of SCN1A found in a dominant epilepsy syndrome disrupt inactivation, thereby producing small persistent inward Na(+) currents that may result in hyperexcitability and seizures.