Noradrenaline Increases K-conductance and Reduces Glutamatergic Transmission in the Mouse Entorhinal Cortex by Activation of α2-Adrenoreceptors

Authors


Correspondence to: Etienne Pralong, as above

Abstract

The entorhinal cortex is a gateway to the hippocampus; it receives inputs from several cortical associative areas as well as subcortical areas. Since there is evidence showing that noradrenaline reduces the epileptic activity generated in the entorhinal cortex, we have examined the action of noradrenaline in the superficial layer of the entorhinal cortex, which is the main source of afferents to the hippocampus. In a previous study we showed that noradrenaline hyperpolarized layer II entorhinal cortex neurons and reduced global synaptic transmission via α2-adrenoreceptors. Here we present a detailed analysis of the effect of noradrenaline on membrane resistance and on the pharmacologically isolated postsynaptic potentials in layer II entorhinal cortex neurons of mice. Noradrenaline (50 μM) hyperpolarized most layer II entorhinal cortex neurons. This hyperpolarization corresponded to an outward current with a reversal potential following the Nernst equilibrium potential for potassium. The hyperpolarizing effect of noradrenaline was blocked by 10 μM yohimbine. These observations suggest that noradrenaline activates a potassium conductance via an α2-adrenoreceptor. Noradrenaline (10–50 μM) reversibly reduced the amplitude of the pharmacologically isolated excitatory potentials mediated by both NMDA and α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors, the former being more strongly affected. Again this effect was blocked by 10 μM yohimbine. In contrast, GABAA-mediated synaptic transmission was virtually unaffected by noradrenaline. Thus, noradrenaline appears to strongly inhibit the glutamate-mediated synaptic transmission in the entorhinal cortex without affecting inhibitory post-synaptic potentials. These observations suggest that α2-adrenergic receptor agonists may exert a beneficial effect in the control of hyperexcitability in temporal lobe epilepsy.

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