Down-regulation of N-type voltage-activated Ca2+ channels by gabapentin

1. Although the cellular and molecular mechanisms of the anticonvulsant action of gabapentin (GBP) remain incompletely described, in vitro studies have shown that GBP binds to the ₂ subunit of the high voltage-activated (HVA) Ca²⁺ channels.2. In this report, we analyzed the effects of GBP on the functional expression of HVA Ca²⁺ channels in the PC12 cell line model system. Negligible inhibition of Ca²⁺ channel activity was observed after acute treatment, but a significant decrease in Ca²⁺ current amplitude was promoted by chronic exposure to GBP.3. Consistent with this, radioligand binding experiments showed a comparable reduction in the total number of membrane HVA N-type channels after GBP treatment.