Seizure Susceptibility Is Associated With Enhanced Intracellular Calcium Release In Rat Inferior Colliculus Neurons Of The Genetically Epilepsy-prone Rat (GEPR-3)
Abstract number :
3.037;
Submission category :
1. Translational Research
Year :
2007
Submission ID :
7783
Source :
www.aesnet.org
Presentation date :
11/30/2007 12:00:00 AM
Published date :
Nov 29, 2007, 06:00 AM
Authors :
P. N'Gouemo1, E. M. Janowski2, N. F. Krusell2, C. L. Faingold3, M. Morad2
Rationale: Intracellular Ca2+ is thought to play an important role in neuronal hyperexcitability that leads to seizures. We have previously reported that high threshold voltage-activated Ca2+ channel current density is markedly enhanced in inferior colliculus (IC) neurons of the genetically epilepsy-prone rats (GEPR-3s), which exhibit inherited seizure susceptibility to auditory stimuli. Whether this inherited seizure susceptibility also alters Ca2+ release from internal Ca2+ stores remains as yet unknown. Here we report on the profiles of intracellular Ca2+ release in IC neurons and their modifications in GEPR-3s. Methods: Adult male Sprague-Dawley rats were used as controls for GEPR-3s. Acutely dissociated neurons of the IC central nucleus were loaded with Ca2+ indicator Fluo-4AM dye and subjected to 2-D confocal imaging at the rate of 33 frames/s. To probe the roles of Ca2+ signaling proteins such as voltage-gated Ca2+ channels, glutamate, ryanodine, and inositol 1,4,5-triphosphate (IP3) receptors, cells were exposed alternatively to 40 mM KCl, 50 μM glutamate, 10-20 mM caffeine, 20 μM ryanodine, 100 μM ATP, 20 μM quisqualate, and 5 µM U73211.Results: Confocal microscopy reveals the presence of somatic Ca2+ transporting proteins in IC neurons of both controls and GEPR-3s. The expression of intracellular Ca2+ transients (ΔF/F0) activated by 40 mM KCl was significantly greater in GEPR-3s compared to controls. In addition, 3-fold increases in IP3-gated but not ryanodine-gated Ca2+ pools were measured in IC neurons of GEPR-3 compared to controls.Conclusions: These findings indicate that inherited seizure susceptibility in GEPR-3s is selectively associated with enhanced intracellular Ca2+ release from IP3-gated Ca2+ pools. It is likely that the increased high threshold voltage-activated Ca2+ channel current is responsible for the upregulation of IP3-gated Ca2+ pools in IC neurons of GEPR-3s. Thus, it is intriguing to speculate that increases in IP3-gated Ca2+ pools may play critical role in this inherited epileptogenesis by enhancing neurotransmitter release. Supported by NIH grants NS047193 (P.N.), AA11628 (C.L.F) and HL16152 (M.M.).
Translational Research