Author(s):
Ambrósio, António F. 
; Silva, Ana P. ; Malva, João O. ; Soares-da-Silva, Patrício ; Carvalho, Arsélio P. ; Carvalho, Caetana M.
Date: 1999
Persistent ID: http://hdl.handle.net/10316/4845
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): Carbamazepine; Glutamate ionotropic receptors; Kainate; Voltage-sensitive Ca2+ channels; Voltage-sensitive Na+ channels; [Ca2+]i
Description
In order to better understand the mechanism(s) of action of carbamazepine (CBZ), we studied its effects on the increase in [Ca2+]i and [Na+]i stimulated by glutamate ionotropic receptor agonists, in cultured rat hippocampal neurons, as followed by indo-1 or SBFI fluorescence, respectively. CBZ inhibited the increase in [Ca2+]i stimulated either by glutamate, kainate, [alpha]-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), or N-methyl--aspartate (NMDA), in a concentration-dependent manner. In order to discriminate the effects of CBZ on the activation of glutamate receptors from possible effects on Ca2+ channels, we determined the inhibitory effects of Ca2+ channel blockers on [Ca2+]i changes in the absence or in the presence of CBZ. The presence of 1 [mu]M nitrendipine, 0.5 [mu]M [omega]-conotoxin GVIA ([omega]-CgTx GVIA), or of both blockers, inhibited the kainate-stimulated increase in [Ca2+]i by 51.6, 32.9 or 68.7%, respectively. In the presence of both 100 [mu]M CBZ and nitrendipine, the inhibition was similar (54.1%) to that obtained with nitrendipine alone, but in the presence of both CBZ and [omega]-CgTx GVIA, the inhibition was greater (54%) than that caused by [omega]-CgTx GVIA alone. However, CBZ did not inhibit the increase in [Na+]i stimulated by the glutamate receptor agonists, but inhibited the increase in [Na+]i due to veratridine. Tetrodotoxin, or MK-801, did not inhibit the influx of Na+ stimulated by kainate, indicating that Na+ influx occurs mainly through the glutamate ionotropic non-NMDA receptors. Moreover, LY 303070, a specific AMPA receptor antagonist, inhibited the [Na+]i response to kainate or AMPA by about 70 or 80%, respectively, suggesting that AMPA receptors are mainly involved. Taken together, the results suggest that CBZ inhibits L-type Ca2+ channels and Na+ channels, but does not inhibit activation of glutamate ionotropic receptors. http://www.sciencedirect.com/science/article/B6T0C-3X1W5Y4-D/1/65c32835840a01052a606b944eb4cabd
