RESUMO
We have investigated using single channel patch-clamp methods potassium channel prevalence in hippocampal neurones from two animal models of AD. Experiments have been carried out on transgenic mice (Tg2576) carrying the Swedish mutation (K670N/M671L) and rats receiving ventricular infusions of okadaic acid. In cell-attached patches from hippocampal neurones from the Tg2576 and control littermate mice there were three principal unitary conductance - 22 pS, 111 pS and 178 pS. The two channels of intermediate and large conductance were voltage-dependent, highly active in cell-attached patches, activity decreasing markedly on hyperpolarisation. The large conductance channel was sensitive to TEA, iberiotoxin, was activated in excised inside-out patches by Ca 2+(i) and is the type I maxi-K+ channel. Significantly, there was a reduction in the prevalence of a TEA-sensitive 113 pS channel in neurones from TG2576 mice with a corresponding increase in prevalence of the maxi-K+ channel. There was no difference in the characteristics of maxi-K+ between patches in neurones from the transgenic and littermate controls. In the rat model single channel analysis was performed on hippocampal neurons from three groups of animals i.e. non-operated, and these receiving an infusion of vehicle or vehicle with okadaic acid. Three principal unitary conductances of around 18 pS, 118 pS and 185 pS were also observed in cell-attached recordings from these three groups. The intermediate and high conductance channels were blocked by TEA or 4-AP or 140 mM RbCl. There were no statistically significant differences in the channel prevalence or channel density between the control and test groups.
Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Canais de Potássio/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos , Hipocampo/citologia , Masculino , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Ácido Okadáico , Técnicas de Patch-Clamp , Canais de Potássio/classificação , Ratos , Ratos Endogâmicos , Ratos Sprague-DawleyRESUMO
Rats with neurotoxic lesions centered in the anterior thalamic nuclei were trained in two versions of a nonspatial, sensory preconditioning procedure. In both versions, two stimulus compounds (AX and BY) were first presented and then X, but not Y, was paired with an aversive unconditioned stimulus. This procedure resulted in greater conditioned responding to A than B. Anterior thalamic lesions had no apparent effect on these two examples of sensory preconditioning, nor did they affect fear conditioning or conditioned taste aversion. In contrast, the same lesions led to a severe deficit on a test of spatial memory. These results help to refine our understanding of the contribution of the anterior thalamic nuclei to spatial memory.