title: Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin.
abstract: The α2δ auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with α2δ1 and α2δ2 subunits and is reported to reduce Ca2+ channel current amplitude (ICa). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record ICa in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of α2δ1-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced ICa and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4-18 h) reduced ICa, and cell surface α2δ1 staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced ICa. These results show that gabapentin has both short-term and long-term mechanisms to reduce ICa 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.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia.
authors.forename: Spring R
authors.initials: SR
authors.lastname: Farrell
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Allison
authors.initials: A
authors.lastname: Sargoy
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia.
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D000077206:Gabapentin; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; C425903:CACNA2D1 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin