Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat.
The inferior colliculus (IC) is the consensus site for seizure initiation in the genetically epilepsy-prone rat (GEPR). We have previously reported that the current density of high threshold voltage-activated (HVA) calcium (Ca(2+)) channels was markedly enhanced in IC neurons of the GEPR-3 (moderate seizure severity substrain of the GEPR). The present study examines whether subunit protein levels of HVA Ca(2+) channels are altered in IC neurons that exhibit enhanced Ca(2+) current density. Quantification shows that the levels of protein expression of the Ca(2+) channel pore-forming alpha1D (L-type) and alpha1E subunits (R-type) were significantly increased in IC neurons of seizure-naive GEPR-3s (SN-GEPR-3s) compared to control Sprague-Dawley (SD) rats. Significant increases and decreases in the levels of protein expression of Ca(2+) channel regulatory beta3 and alpha2delta subunits occurred in IC neurons of SN-GEPR-3s compared to control SD rats, respectively. No changes occurred in the protein expression of Ca(2+) channel pore-forming alpha1A (P/Q-type), alpha1B (N-type) and alpha1C (L-type) subunits in IC neurons of SN-GEPR-3s compared to control SD rats. A single seizure selectively enhanced protein expression of Ca(2+) channel alpha1A subunits in IC neurons of GEPR-3s. Thus, up-regulation of Ca(2+) channel alpha1D and alpha1E subunits may represent the molecular mechanisms for the enhanced current density of L- and R-type of HVA Ca(2+) channels in IC neurons of the GEPR, and may contribute to the genetic basis of their enhanced seizure susceptibility. The up-regulation of Ca(2+) channel alpha1A subunits induced by seizures may contribute to the increasing IC neuronal excitability that results from repetitive seizures in the GEPR.
N'Gouemo
Prosper
P
Department of Pediatrics and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. pn@georgetown.edu
Yasuda
Robert
R
Faingold
Carl L
CL
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D007245:Inferior Colliculi / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015220:Calcium Channels