Calcium channel dysfunction in inferior colliculus neurons of the genetically epilepsy-prone rat.
Voltage-gated calcium (Ca(2+)) channels are thought to play an important role in epileptogenesis and seizure generation. Here, using the whole cell configuration of patch-clamp techniques, we report on the modifications of biophysical and pharmacological properties of high threshold voltage-activated Ca(2+) channel currents in inferior colliculus (IC) neurons of the genetically epilepsy-prone rats (GEPR-3s). Ca(2+) channel currents were measured by depolarizing pulses from a holding potential of - 80 mV using barium (Ba(2+)) as the charge carrier. We found that the current density of high threshold voltage-activated Ca(2+) channels was significantly larger in IC neurons of seizure-naive GEPR-3s compared to control Sprague-Dawley rats, and that seizure episodes further enhanced the current density in the GEPR-3s. The increased current density was reflected by both a - 20 mV shifts in channel activation and a 25% increase in the non-inactivating fraction of channels in seizure-naive GEPR-3s. Such changes were reduced by seizure episodes in the GEPR-3s. Pharmacological analysis of the current density suggests that upregulation of L-, N- and R-type of Ca(2+) channels may contribute to IC neuronal hyperexcitability that leads to seizure susceptibility in the GEPR-3s.
N'gouemo
Prosper
P
Department of Pediatrics, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC 20057, United States. pn@georgetown.edu
Faingold
Carl L
CL
Morad
Martin
M
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels