Link Between Absence Seizures and T-Type Calcium Channels
An animal model of human absence epilepsy containing a G to C mutation of the Cav3.2 T-type Ca2+ channel gene (Cacna1h) ties together the gene mutation, increased T-type Ca2+ channel activity and the epileptic phenotype. Mice lacking a related gene (Cacna1a) also show enhanced T-type Ca2+ current and increased susceptibility to absence seizures. On the other hand, mutations that decrease T-type Ca2+ channel activity in thalamocortical relay neurons display no spike–wave discharges associated with absence seizures. These animal models are supported by genetic studies showing defects in T-type Ca2+ channel function in humans suffering from epilepsy. Thus, in both human and animal studies, T-type Ca2+ channel antagonists show promise in the treatment of absence seizures.
KeywordsAbsence Seizure Absence Epilepsy Wave Discharge Juvenile Myoclonic Epilepsy Burst Firing
We thank Peggy Mankin and Hongyi Chen for manuscript preparation. This work was funded by the Pediatrics Department fund, Children’s Hospital of Illinois.
- Broicher T, Seidenbecher T, Meuth P, Munsch T, Meuth SG, Kanyshkova T, Pape HC, Budde T (2007) T-current related effects of antiepileptic drugs and a Ca2+ channel antagonist on thalamic relay and local circuit interneurons in a rat model of absence epilepsy. Neuropharmacology 53:431–446PubMedCrossRefGoogle Scholar
- Powell KL, Cain SM, Ng C, Sirdesai S, David LS, Kyi M, Garcia E, Tyson JR, Reid CA, Bahlo M, Foote SJ, Snutch TP, O'Brien TJ (2009) A Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. J Neurosci 29:371–380PubMedCrossRefGoogle Scholar
- Rajakulendran S, Graves TD, Labrum RW, Kotzadimitriou D, Eunson L, Davis MB, Davies R, Wood NW, Kullmann DM, Hanna MG, Schorge S (2010) Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy. J Physiol 588:1905–1913PubMedCentralPubMedCrossRefGoogle Scholar
- Tringham E, Powell KL, Cain SM, Kuplast K, Mezeyova J, Weerapura M, Eduljee C, Jiang X, Smith P, Morrison JL, Jones NC, Braine E, Rind G, Fee-Maki M, Parker D, Pajouhesh H, Parmar M, O’Brien TJ, Snutch TP (2012) T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures. Sci Transl Med 4:121ra19PubMedCrossRefGoogle Scholar