Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel

The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and promotion of oscillatory neuronal activities. However, the origin and molecular basis of the persistent current have remained controversial for decades. Here, we provide direct evidence that U-to-C RNA editing of an insect sodium channel transcript generates a sodium channel with a persistent current. We detected a persistent TTX-sensitive current in a splice variant of the cockroach sodium channel gene BgNa(v) (formerly para(CSMA)). Site-directed mutagenesis experiments revealed that an F-to-S change at the C-terminal domain of this variant was responsible for the persistent current. We demonstrated that this F-to-S change was the result of a U-to-C RNA editing event, which also occurred in the Drosophila para sodium channel transcript. Our work provides direct support for the hypothesis that posttranscriptional modification of a conventional transient sodium channel produces a persistent TTX-sensitive sodium channel.