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

The alpha (2) delta auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with alpha (2) delta (1) and alpha (2) delta (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 alpha (2) delta (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 alpha (2) delta (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.