TY - JOUR T1 - Differential Effect of Gabapentin on Neuronal and Muscle Calcium Currents JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 727 LP - 735 VL - 297 IS - 2 AU - Kris J. Alden AU - Jesús Garcı́a Y1 - 2001/05/01 UR - http://jpet.aspetjournals.org/content/297/2/727.abstract N2 - Calcium channels modulate cell function by controlling Ca2+influx. A main component of these proteins is the α2/δ subunit. Nevertheless, how this subunit regulates channel activity in situ is unclear. Gabapentin (GBP), an analgesic and anti-epileptic agent with an unknown mechanism of action, specifically binds to the α2/δ subunit. Using the patch clamp technique, we tested the effects of GBP on Ca2+ currents from dorsal root ganglion (DRG) cells, the mediators of pain perception, to determine how GBP binding modifies channel activity. In DRGs, GBP significantly reduced whole cell Ca2+ current amplitude at positive membrane potentials when a pulse preceded the test pulses or when cells were stimulated with a train of pulses. In control cells, neither prepulse depolarization nor pulse trains reduced Ca2+ currents at positive potentials. GBP did not reduce the low-voltage activated Ca2+ current under any experimental condition. Similar to DRG cells, GBP attenuated Ca2+ current in skeletal myotubes at positive membrane potentials in the presence of a depolarizing prepulse. However, GBP did not significantly alter Ca2+ currents in cardiac myocytes. Reverse transcription-polymerase chain reaction was used to confirm expression of the α2/δ subunit in these cells. Each cell type expressed multiple isoforms of α2/δ. Muscle cells showed a more variable expression of α2/δ subunits than did DRG cells. Our results suggest a possible participation of the α2/δ subunit in the action of GBP. Our data also indicate that GBP inhibits Ca2+ channels in a use- and voltage-dependent manner at a therapeutically relevant concentration. The American Society for Pharmacology and Experimental Therapeutics ER -