Long‐term regulation of voltage‐gated Ca2+ channels by gabapentin

Abstract

Gabapentin (GBP) is a γ‐aminobutyric acid analog effective in the treatment of seizures. A high‐affinity interaction between GBP and the α₂δ subunit of the voltage‐gated Ca²⁺ channels has been documented. In this report, we examined the effects of the chronic treatment with GBP on neuronal recombinant P/Q‐type Ca²⁺ channels expressed in Xenopus oocytes. GBP did not affect significantly the amplitude or the voltage dependence of the currents. Exposure to the drug did, however, slow down the kinetics of inactivation in a dose‐dependent fashion. In addition, biochemical analysis showed that the integrity of Ca²⁺ channel complex is not apparently affected by GBP binding, suggesting that chronic treatment with the drug might cause the channel kinetic modification through subtle conformational changes of the protein complex.