Neurobiology of Disease 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
نویسندگان
چکیده
Kim L. Powell,1* Stuart M. Cain,2* Caroline Ng,1 Shreerang Sirdesai,1 Laurence S. David,2 Mervyn Kyi,1 Esperanza Garcia,2 John R. Tyson,2 Christopher A. Reid,3 Melanie Bahlo,4 Simon J. Foote,5 Terrance P. Snutch,2 and Terence J. O’Brien1 1Departments of Medicine, Surgery, and Neurology, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria 3050, Australia, 2Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4, 3Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia, 4The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia, and 5Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7000, Australia
منابع مشابه
Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility.
T-type calcium channels play essential roles in regulating neuronal excitability and network oscillations in the brain. Mutations in the gene encoding Cav3.2 T-type Ca(2+) channels, CACNA1H, have been found in association with various forms of idiopathic generalized epilepsy. We and others have found that these mutations may influence neuronal excitability either by altering the biophysical pro...
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Heron and colleagues (Ann Neurol 2004;55:595-596) identified three missense mutations in the Cav3.2 T-type calcium channel gene (CACNA1H) in patients with idiopathic generalized epilepsy. None of the variants were associated with a specific epilepsy phenotype and were not found in patients with juvenile absence epilepsy or childhood absence epilepsy. Here, we introduced and functionally charact...
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CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily i...
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