Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic α 2-adrenoceptors

Abstract

It has been shown that noradrenergic activation has great influence on the activities of hypothalamic supraoptic neurons. No direct evidence has been reported on the presynaptic effects of adrenoceptors in the actions of noradrenaline on supraoptic neurons, although postsynaptic mechanisms have been studied extensively. In the present study, we explored presynaptic effects of noradrenaline on the supraoptic neurons by measuring spontaneous inhibitory postsynaptic currents (IPSC) with the whole-cell patch-clamp technique. Noradrenaline reduced the frequency of IPSCs in a dose-dependent (10 −9 to 10 −3 M) and reversible manner. Noradrenaline did not affect the amplitude of IPSCs at concentrations of 10 −9 to 10 −5 M, but reduced the amplitude of IPSCs at high concentrations (10 −4 and 10 −3 M). The inhibitory effects of noradrenaline were mimicked by the α 2-agonist clonidine (10 −4 M), but not by the α 1-agonist methoxamine (10 −4 M) nor by the β-agonist isoproterenol (10 −4 M). Moreover, the inhibitory effects of noradrenaline on IPSCs were blocked by the non-selective α antagonist phentolamine (10 −4 M) or the selective α 2-antagonist yohimbine (10 −4 M), but not by the α 1-antagonist prazosin (10 −4 M). These results suggest that noradrenaline inhibits release of GABA from the presynaptic GABAergic terminals of the supraoptic neurons by activating presynaptic α 2-adrenoceptors and such presynaptic mechanisms may play a role in the excitatory control of SON neurons by noradrenergic neurons.