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Glutamate‐induced internalization of Ca v 1.3 L‐type Ca 2+ channels protects retinal neurons against excitotoxicity
Author(s) -
Mizuno Fengxia,
Barabas Peter,
Krizaj David,
Akopian Abram
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.181305
Subject(s) - excitotoxicity , kainate receptor , internalization , glutamate receptor , microbiology and biotechnology , biology , neuroscience , chemistry , biochemistry , ampa receptor , receptor
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.