Mecanismo de ação do brometo de sódio em fatias de hipocampo de ratos

• Ano de defesa: 2011
• Autor(a) principal: Carlesso, Fernanda Noal
• Orientador(a): Costa, Jaderson Costa da
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul; Porto Alegre
• Palavras-chave em Português: MEDICINA; EPILEPSIA; ANTICONVULSIVOS; MEDICAMENTOS; HIPOCAMPO; ANIMAIS DE LABORATÓRIO; RATOS - EXPERIÊNCIAS
• Link de acesso: http://hdl.handle.net/10923/4583

Sodium bromide, first-generation antiepileptic drug, is still used to treat refractory epilepsy in children. Its mechanism is not fully elucidated. In this work, i-investigate its actions on the epileptiform activity (EA's) of non-synaptic region of the dentate gyrus in vitro, ii-compare his action with a solution containing high concentration of sodium chloride; blocker of chloride channels voltage dependent (SITS, DIDS), iii-investigate the possible involvement of gap junctions at the time of action of the drug. The study involved experimental measurements such as extracellular field records and computer simulations. AE'S returned inhibition induced model of zero calcium and high potassium with 9 mM NaBr (n=6). With the perfusion of calcium solution zero high concentration of NaCl in the records (n=6) obtained a field transient blockage. We compared the effect of NaBr with chloride channel blockers of voltage-dependent (DIDS 250 μM, n=8 and SITS 1 mM, n=3), we obtained a similarity in the records of extracellular field potential, suggesting a possible involvement of chloride channels voltage dependent. The blocker of gap junctions (N-octanol) at concentrations of 0,07 mM was used with 5 mM bromide. This reduced the high frequency elucidated in the transient period during drug application. The effect of Br- isn´t just in membrane potential, through its greater permeability compared to the Cl- inducing hyperpolarization, but also show a higher permeability to the chloride channels voltage-dependent. The increased frequency of discharges can be due to the competitive effect of Br- on chloride channels, reducing the permeability to Cl-. The NaBr has a little affinity for the cotransporter NKCC1 and partially replacing Cl- in cotransporter KCC2. The origin of high frequency in records with bromide, is probably related with the gaps junctions.