Autor(es):
Rombo, Diogo Miguel Santos 
Data: 2009
Identificador Persistente: http://hdl.handle.net/10451/1511
Origem: Repositório da Universidade de Lisboa
Assunto(s): Biologia celular; Neurobiologia; Adenosina; Teses de mestrado
Descrição
Tese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de Ciências Resumo alargado em português disponível no documento Much of what is known about the modulatory role of adenosine in the hippocampus is on glutamatergic communication and presynaptic GABAergic function. However, any possible role of adenosine on responses of the postsynaptic cell to GABA had not been evaluated. The effect of A1 and A2A receptor activation on inhibitory postsynaptic currents (PSCs) mediated by GABAA receptors was now examined in CA1 pyramidal neurons of young (3-5 weeks) rat hippocampal slices by using the whole-cell patch-clamp technique (Vh=-80mV). GABAA-mediated currents were evoked through pressure application of muscimol (30µM), a GABAA receptor agonist, directly to the cell soma. Bath application of a selective A2A receptor agonist, CGS 21680 (30nM), induced no statistically significant differences on muscimol-evoked currents (101%±2,1% of baseline, n=6, p=0,715). The superfusion of the adenosine A1 receptor agonist, CPA (10-30nM), significantly decreased the peak amplitude of GABAergic responses with a maximum effect (to 54%±3,9% of pre-control value, n=12, p<0.0001) observed within 45 min after its application. This effect of CPA was not reversible within 40min after washing it out from the bath. However, the application of DPCPX (50nM), an adenosine A1 receptor antagonist, induced the recovery of the PSCs towards 84%±6,5% of pre-control value (n=3, p<0,001 compared with CPA (10nM)). Pre-incubation with DPCPX (100nM) also blocked the effect of CPA (30nM) on GABAA receptor currents (100%±0,6% of the baseline, n=5, p=0,503) and unmasked the inhibition of PSCs by endogenous extracellular adenosine (113%±1,0% to 100%±0,6%, n=5, p<0,001). This phenomenon is independent of excitatory inputs arriving to pyramidal CA1 neurons since the CPA effect was maintained (to 60%±8,3%, n=4, p<0,05) in the presence of blockers of excitatory transmission (CNQX (10µM); DL-AP5 (50µM); TTX (500nM)). Together, these results suggest that postsynaptic GABAA-mediated currents are modulated by adenosine A1, but not A2A receptor, in rat hippocampal CA1 pyramidal cells.
Tipo de Documento
Dissertação de Mestrado
Orientador(es)
Sebastião, Ana Maria Ferreira de Sousa; Ramos, Margarida,
