Published online by Cambridge University Press: 23 December 2013
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.