Long-term regulation of voltage-gated Ca(2+) channels by gabapentin.
Gabapentin (GBP) is a gamma-aminobutyric acid analog effective in the treatment of seizures. A high-affinity interaction between GBP and the alpha(2)delta subunit of the voltage-gated Ca(2+) channels has been documented. In this report, we examined the effects of the chronic treatment with GBP on neuronal recombinant P/Q-type Ca(2+) 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 Ca(2+) 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.
Kang
Myoung-Goo
MG
Howard Hughes Medical Institute, Department of Physiology and Biophysics, The University of Iowa College of Medicine, 400 Eckstein Medical Research Building, Iowa City 52242, USA.
Felix
Ricardo
R
Campbell
Kevin P
KP
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids; D005260:Female; D000077206:Gabapentin; D066298:In Vitro Techniques; D007700:Kinetics; D009865:Oocytes / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D003509:Cyclohexanecarboxylic Acids; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin