Genetic Studies on the Role of T-Type Ca2+ Channels in Sleep and Absence Epilepsy

Abstract

Thalamocortical neurons in mammals fire action potentials in two different modes, burst or tonic, depending on the cellular state. The burst firing is driven by the low threshold Ca2+ spike that is generated by Ca2+ influx through T-type Ca2+ channels, and has long been implicated in the pathogenesis of absence epilepsy and the regulation of sleep rhythms. The recent availability of the knock-out mice for the alpha 1G locus, encoding the predominant form of T-type channels in thalamocortical neurons, has provided an opportunity to examine those ideas at the level of organism. In this review we will describe recent results demonstrating the essential role of thalamic bursts in certain forms of absence seizures and in some of the sleep rhythms. Available information so far reveals the sensory gating role of thalamic bursts, and thus of alpha 1G T-type channels. Understanding of the molecular targets involved in pathophysiological mechanisms will help develop drugs to control those pathological states.