Calcium channel dysfunction in inferior colliculus neurons of the genetically epilepsy-prone rat

NEUROPHARMACOLOGY

卷:56

Article

N'Gouemo, Prosper¹  Faingold, Carl L.²  Morad, Martin³ 

[1] Georgetown Univ, Dept Pediat, Med Ctr, Washington, DC 20057 USA

[2] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA

[3] Georgetown Univ, Dept Pharmacol, Med Ctr, Washington, DC 20057 USA

关键词: Ca2+ channel current;    L-type;    N-type;    R-type;    Reflex audiogenic seizure;   

DOI  :  10.1016/j.neuropharm.2008.11.005

来源: Elsevier

【 摘 要 】

Voltage-gated calcium (Ca2+) 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 Ca2+ channel currents in inferior colliculus (IC) neurons of the genetically epilepsy-prone rats (GEPR-3s). Ca2+ channel currents were measured by depolarizing pulses from a holding potential of -80 mV using barium (Ba2+) as the charge carrier. We found that the current density of high threshold voltage-activated Ca2+ 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 Ca2+ channels may contribute to IC neuronal hyperexcitability that leads to seizure susceptibility in the GEPR-3s. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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