Preferential potentiation by nitric oxide of spontaneous inhibitory postsynaptic currents in rat supraoptic neurones

Magnocellular neurones in the supraoptic nucleus and paraventricular nucleu s express mRNA for nitric oxide synthase (NOS) and the expression becomes m ore prominent when the release of vasopressin or oxytocin is stimulated. It has also been reported that NO donors inhibit the electrical activity of s upraoptic nucleus neurones, but the mechanism involved in the inhibition re mains unclear. In the present study, to know whether modulation of synaptic inputs into supraoptic neurones is involved in the inhibitory effect of NO , we measured spontaneous excitatory and inhibitory postsynaptic currents ( EPSCs and IPSCs) from rat supraoptic nucleus neurones in slice preparations identified under a microscope using the whole-cell mode of the slice-patch -clamp technique. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), rev ersibly increased the frequency of spontaneous IPSCs mediated by GABA(A) re ceptors, without affecting the amplitude, indicating that NO potentiated IP SCs via a presynaptic mechanism. The NO scavenger, haemoglobin, suppressed the potentiation of IPSCs by SNAP. On the other hand, SNAP did not cause si gnificant effects on EPSCs mediated by non-NMDA glutamate receptors. The me mbrane permeable analogue of cGMP, 8-bromo cGMP, caused a significant reduc tion in the frequency and amplitude of both IPSCs and EPSCs. The results su ggest that NO preferentially potentiates the inhibitory synaptic inputs int o supraoptic nucleus neurones by acting on GABA terminals in the supraoptic nucleus, possibly via a cGMP-independent mechanism. The potentiation may, at least in part, account for the inhibitory action of NO on the neural act ivity of supraoptic neurones.