Histamine suppresses non-NMDA excitatory synaptic currents in rat supraoptic nucleus neurons

Whole cell patch-clamp recordings were obtained from supraoptic neurons to investigate the effects of histamine on excitatory postsynaptic currents ev oked by electrical stimulation of areas around the posterior supraoptic nuc leus. When cells were voltage-clamped at -70 mV, evoked excitatory postsyna ptic currents had amplitudes of 88.4 +/- 9.6 pA and durations of 41.1 +/- 3 .0 ms (mean +/- SE; n = 43). With twin stimulus pulses (20 Hz) used, paired -pulse facilitation ratios were 1.93 +/- 0.12. Bath application of 6-cyano- 7-nitroquinoxalene-2,3-dione (CNQX) abolished synaptic currents. Histamine at concentrations similar to 0.1-10 mu M reversibly suppressed excitatory p ostsynaptic currents in all supraoptic neurons tested. Within 2 min after a pplication of (10 mu M) histamine, current amplitudes and durations decreas ed by 61.5 and 31.0%, respectively, with little change in the paired-pulse facilitation ratio. Dimaprit or imetit (H-2 or H-3 receptor agonists) did n ot reduce synaptic currents, whereas pyrilamine (H-1 receptor antagonist) b locked histamine-induced suppression of synaptic currents. When patch elect rodes containing guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) were used to record cells, histamine still suppressed current amplitudes by 49.1% and durations by 41.9%. Similarly, intracellular diffusion of bis-(o-aminophen oxy)-N,N,N',N'-tetraacetic acid (BAPTA) and H-7 did not abolish histamine-i nduced suppression of synaptic currents, either. Bath perifusion of 8-bromo -quanosine 3',5'- cyclic monophosphate reduced current amplitudes by 32.3% and durations by 27.9%. After bath perfusion of slices with N-omega-nitro-L -arginine methyl ester (L-NAME), histamine injection decreased current ampl itudes only by 31.9%, much less than the inhibition rate in control (P < 0. 01). In addition, histamine induced little change in current durations and paired-pulse facilitation ratios, representing a partial blockade of histam ine effects on synaptic currents by L-NAME. In supraoptic neurons recorded using electrodes containing BAPTA and perifused with L- NAME, the effects o f histamine on synaptic currents were completely abolished. Norepinephrine injection reversibly decreased current amplitudes by 39.1% and duration by 64.5%, with a drop in the paired-pulse facilitation ratio of 47.9%. Bath pe rifusion of L-NAME, as well as intracellular diffusion of GDP-beta-S,, 1 -( 5-isoquinolinylsulfonyl)-2-methyl-piperazine, or BAPTA, failed to block nor epinephrine-induced suppression of evoked synaptic currents. The present re sults suggest that histamine suppresses non-N-methyl-D-aspartate synaptic c urrents in supraoptic neurons through activation of H-1 receptors. It is po ssible that histamine first acts at supraoptic cells (perhaps both neuronal and nonneuronal) and induces the production of nitric oxide, which then di ffuses to nearby neurons and modulates synaptic transmission by a postsynap tic mechanism.