Voltage-Gated Calcium Channels in Epilepsy

Excerpt

Voltage-gated calcium channels mediate calcium influx that both controls neuronal excitability and regulates calcium-sensitive intracellular signalling pathways. While the substrates underlying epileptic seizures remain to be fully understood, burst-firing in the thalamocortical circuitry is known to be evoked by activation of low-voltage-activated (T-type) calcium channels and is thought to give rise to spike-wave discharges associated with absence epilepsy. Naturally occurring rodent genetic models of absence epilepsy have revealed that at least the Ca_V3.1 and Ca_V3.2 T-type channel isoforms play critical roles in disease etiology. Additionally, altered expression of several calcium channel subtypes has been observed and gain-of-function mutations have been identified in calcium channel genes from both epilepsy patients and animal models of epilepsy further providing useful tools for elucidating the underlying involvement of calcium channels towards disease pathophysiology. A number of the currently prescribed anti-epileptic drugs have been shown to inhibit calcium channel activity although these agents typically interact with multiple molecular targets. Given their unique distributions and contributions to higher brain functions, the selective pharmacological blockade of T-type calcium channel subtypes may provide attractive targets for the development of future therapeutic treatments.