Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/4845
Title: Carbamazepine inhibits L-type Ca2+ channels in cultured rat hippocampal neurons stimulated with glutamate receptor agonists
Authors: Ambrósio, António F. 
Silva, Ana P. 
Malva, João O. 
Soares-da-Silva, Patrício 
Carvalho, Arsélio P. 
Carvalho, Caetana M. 
Keywords: Carbamazepine; Glutamate ionotropic receptors; Kainate; Voltage-sensitive Ca2+ channels; Voltage-sensitive Na+ channels; [Ca2+]i
Issue Date: 1999
Citation: Neuropharmacology. 38:9 (1999) 1349-1359
Abstract: 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.
URI: http://hdl.handle.net/10316/4845
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
file0a433b4aa20944869326bfa62c3195c1.pdf194.42 kBAdobe PDFView/Open
Show full item record

Page view(s) 50

367
checked on Jan 20, 2020

Download(s) 50

269
checked on Jan 20, 2020

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.