Author/Editor | Mizuno, Fenxia; Barabas, Peter; Križaj, David; Akopian, Abram | |
Title | Glutamate-induced internalization of Ca(v)1.3 L-type Ca(2+) channels protects retinal neurons against excitotoxicity | |
Type | članek | |
Source | J Physiol | |
Vol. and No. | Letnik 588, št. 6 | |
Publication year | 2010 | |
Volume | str. 953-66 | |
Language | eng | |
Abstract | Glutamate-induced rise in the intracellular Ca(2+) level is thought to be a major cause of excitotoxic cell death, but the mechanisms that control the Ca(2+) overload are poorly understood. Using immunocytochemistry, electrophysiology and Ca(2+) imaging, we show that activation of ionotropic glutamate receptors induces a selective internalization of Ca(v)1.3 L-type Ca(2+) channels in salamander retinal neurons. The effect of glutamate on Ca(v)1.3 internalization was blocked in Ca(2+)-free external solution, or by strong buffering of internal Ca(2+) with BAPTA. Downregulation of L-type Ca(2+) channel activity in retinal ganglion cells by glutamate was suppressed by inhibitors of dynamin-dependent endocytosis. Stabilization of F-actin by jasplakinolide significantly reduced the ability of glutamate to induce internalization suggesting it is mediated by Ca(2+)-dependent reorganization of actin cytoskeleton. We showed that the Ca(v)1.3 is the primary L-type Ca(2+) channel contributing to kainate-induced excitotoxic death of amacrine and ganglion cells. Block of Ca(v)1.3 internalization by either dynamin inhibition or F-actin stabilization increased vulnerability of retinal amacrine and ganglion cells to kainate-induced excitotoxicity. Our data show for the first time that Ca(v)1.3 L-type Ca(2+) channels are subject to rapid glutamate-induced internalization, which may serve as a negative feedback mechanism protecting retinal neurons against glutamate-induced excitotoxicity. | |
Descriptors | ANIMALS CYTOSKELETON GLUTAMIC ACID PATCH-CLAMP TECHNIQUES RECEPTORS, GLUTAMATE URODELA |