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 alpha2delta 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.
D000085:Acetates / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000588:Amines; D027062:Amino Acid Transport System L / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077206:Gabapentin; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives; D020960:omega-Conotoxins / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D027062:Amino Acid Transport System L; D000927:Anticonvulsants; D020864:Calcium Channels, N-Type; D003509:Cyclohexanecarboxylic Acids; D020960:omega-Conotoxins; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D002118:Calcium