Title

Metabotropic glutamate receptor 5 and calcium signaling in retinal amacrine cells

Document Type

Article

Publication Date

8-5-2002

Abstract

To begin to understand the modulatory role of glutamate in the inner retina, we examined the mechanisms underlying metabotropic glutamate receptor 5 (mGluR5)-dependent Ca2+ elevations in cultured GABAergic amacrine cells. A partial sequence of chicken retinal mGluR5 encompassing intracellular loops 2 and 3 suggests that it can couple to both Gq and Gs. Selective activation of mGluR5 stimulated Ca2+ elevations that varied in waveform from cell to cell. Experiments using high external K+ revealed that the mGluR5-dependent Ca2+ elevations are distinctive in amplitude and time course from those engendered by depolarization. Experiments with a Ca2+-free external solution demonstrated that the variability in the time course of mGluR5-dependent Ca2+ elevations is largely due to the influx of extracellular Ca2+. The sensitivity of the initial phase of the Ca2+ elevation to thapsigargin indicates that this phase of the response is due to the release of Ca2+ from the endoplasmic reticulum. Pharmacological evidence indicates that mGluR5-mediated Ca2+ elevations are dependent upon the activation of phospholipase C. We rule out a role for L-type Ca2+ channels and cAMP-gated channels as pathways for Ca2+ entry, but provide evidence of transient receptor potential (TRP) channel-like immunoreactivity, suggesting that Ca2+ influx may occur through TRP channels. These results indicate that GABAergic amacrine cells express an avian version of mGluR5 that is linked to phospholipase C-dependent Ca2+ release and Ca2+ influx, possibly through TRP channels.

Publication Source (Journal or Book title)

Journal of Neurochemistry

First Page

973

Last Page

983

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