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Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin

Published online by Cambridge University Press:  23 December 2013

SPRING R. FARRELL
Affiliation:
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia
ALLISON SARGOY
Affiliation:
Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California
NICHOLAS C. BRECHA
Affiliation:
Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Department of Medicine, Jules Stein Eye Institute, and CURE Digestive Diseases Research Center, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Veterans Administration Greater Los Angeles Health System, Los Angeles, California
STEVEN BARNES*
Affiliation:
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Veterans Administration Greater Los Angeles Health System, Los Angeles, California Neuroscience Institute and Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia

Abstract

The α 2 δ auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with α 2 δ 1 and α 2 δ 2 subunits and is reported to reduce Ca2+ channel current amplitude (I Ca). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record I Ca in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of α 2 δ 1-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced I Ca and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4–18 h) reduced I Ca, and cell surface α 2 δ 1 staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced I Ca. These results show that gabapentin has both short-term and long-term mechanisms to reduce I Ca in isolated RGCs. Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 2013 

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