Baclofen inhibits with high affinity an L-type-like voltage-dependent calcium channel in cerebellar granule cell cultures.
In primary cultures of cerebellar granule cells, D,L baclofen (p-chlorophenyl-GABA) inhibited approximately 50% of the calcium-45 influx induced with cell depolarization. The half maximal effective concentration for baclofen was 4 nM. Basal calcium influx was not influenced by baclofen thus suggesting that its inhibitory action could be exerted via a voltage dependent calcium channel (VDCC). Whole-cell recordings by patch-clamp technique showed a calcium current that appeared to be similar to the reported L-type VDCC. Nanomolar concentrations of baclofen also inhibited this calcium current by about 60%. However, in order for baclofen to be active, it needed to be placed into the incubation buffer at least five minutes before patching a cell raising the possibility that baclofen may be acting to inhibit the VDCC via a second messenger system.
Wojcik
W J
WJ
Fidia Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, D.C. 20007.
Travagli
R A
RA
Costa
E
E
Bertolino
M
M
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects
D015220:Calcium Channels; D001418:Baclofen; D002118:Calcium