T type calcium channel absence epilepsy

T-type calcium channels in seizures and epileptogenesis. It is currently estimated that around 50 million people in the world.

It is currently estimated that around 50 million people in the world.

T type calcium channel absence epilepsy. The thalamic relay neurons reticular thalamic nucleus and neocortical pyramidal cells form a circuit that sustains oscillatory burst firing and is regarded as the underlying mechanism of absence seizures. T-type calcium channels play a key role in this circuit. Here we review the role of T-type calcium channel genes in the development of absence seizures and emphasize gain or loss of function mutations.

Absence epilepsy accompanies the paroxysmal oscillations in the thalamocortical circuit referred as spike and wave discharges SWDs. Low-threshold burst firing mediated by T-type Ca 2 channels highly expressed in both inhibitory thalamic reticular nuclei TRN and excitatory thalamocortical TC neurons has been correlated with the generation. We investigated whether the T-type calcium channel gene alpha 1G is associated with childhood absence epilepsy CAE a form of idiopathic generalized epilepsy.

We carried out direct sequencing of exons 1-37 and the exon-intron boundaries of the alpha 1G gene in 48 Han Chinese patients with CAE and 48 normal controls. We found no mutation in the exons of alpha 1G. The function of T-type channels in TRN neurons in the genesis of absence epilepsy can be elucidated through the analysis of Ca V 32 and Ca V 33 T-type Ca 2 channels which are expressed in TRN neurons but not in TC neurons.

The most direct demonstration for the role of T-type channels and burst firing among TRN neurons in the generation of absence seizures can be provided by selective. T-type calcium channels in seizures and epileptogenesis. T-type calcium channels are believed to play a critical role in the generation of the hypersynchronous oscillatory thalamocortical activity that underlies absence seizures and of the intrinsic burst firing of hippocampal pyramidal neurons in TLE.

T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures. Absence seizures are a common seizure type in children with genetic generalized epilepsy and are characterized by a temporary loss of awareness arrest of physical activity and accompanying spike-and-wave discharges on an electroencephalogram. The three T-type calcium channels Ca v 31 Ca v 32 and Ca v 33 are widely but differentially expressed in the thalamocortical circuitry implicated in absence seizures.

The role of T-type channels in absence epilepsies is also highlighted by the anticonvulsive effects of ethosuximide an inhibitor of T-type Ca 2 currents in the treatment of absence seizures Coulter et al 1989. Recent insights provided by the identification of mutations in the PQ-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review we consider how genetic variation in neuronal.

Low voltage-activated T-type calcium channels underlie the burst-firing associated with spike-and-wave discharges observed on electroencephalography. Childhood absence epilepsy CAE a subtype of idiopathic generalized epilepsy IGE is characterized by bihemispheric 3Hz spikeandwave discharges SWDs that are known to involve Ttype calcium channels expressed in the thalamocortical network 1. The Genetic Absence Epilepsy Rats from Strasbourg.

T-type calcium channels have been implicated to play a role in the modulation of anxiety as Cav32 deficient mice display an elevated anxiety-like phenotype in a lightdark conflict test EPM and open field test. The current study is the first to directly examine the effects of a T-type calcium channel antagonist on anxiety-like behavior. It is well established that idiopathic generalized epilepsies IGEs show a polygenic origin and may arise from dysfunction of various types of voltage- and ligand-gated ion channels.

There is an increasing body of literature implicating both high- and low-voltage-activated HVA and LVA calcium channels and their ancillary subunits in IGEs. Cav21 PQ-type calcium channels control synaptic transmission at. The ability of the T-type calcium channel antagonists to inhibit absence seizures and reduce the duration and cycle frequency of spike-and-wave discharges also suggests that T-current generated by T-type calcium channels is a key component in the formation of absence seizures.

T-type calcium channels and burst-firing in absence epilepsy Further evidence implicating burst-firing in seizures is observed in rodents with either genetically-induced or spontaneously-acquired epileptic phenotypes 41 50. As different brain regions interact in cycle one excites the next until they become locked into a self-propagating loop. Low voltage-activated T-type calcium channels underlie the burst-firing associated with spike-and-wave discharges observed on electroencephalography recordings during certain forms of epileptic seizures.

It is currently estimated that around 50 million people in the world. Ttype calcium channels in seizures and epileptogenesis. Ttype calcium channels are believed to play a critical role in the generation of the hypersynchronous oscillatory thalamocortical activity that underlies absence seizures 37-39 and of the intrinsic burst firing of hippocampal pyramidal neurons in TLE 40-42.

In addition T-type Ca 2 channels are implicated in the action of certain anti-absence seizure drugs 14 16. Several lines of evidence have implicated the Ca V.