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 evoked by electrical stimulation of areas around the posterior supraoptic nucleus. When cells were voltage-clamped at -70 mV, evoked excitatory postsynaptic 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 approximately 0.1-10 microM reversibly suppressed excitatory postsynaptic currents in all supraoptic neurons tested. Within 2 min after application of (10 microM) histamine, current amplitudes and durations decreased 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 not reduce synaptic currents, whereas pyrilamine (H(1) receptor antagonist) blocked histamine-induced suppression of synaptic currents. When patch electrodes 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-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) and H(7) did not abolish histamine-induced 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 amplitudes 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 histamine effects on synaptic currents by L-NAME. In supraoptic neurons recorded using electrodes containing BAPTA and perifused with L-NAME, the effects of 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 perifusion of L-NAME, as well as intracellular diffusion of GDP-beta-S, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine, or BAPTA, failed to block norepinephrine-induced suppression of evoked synaptic currents. The present results suggest that histamine suppresses non-N-methyl-D-aspartate synaptic currents in supraoptic neurons through activation of H(1) receptors. It is possible that histamine first acts at supraoptic cells (perhaps both neuronal and nonneuronal) and induces the production of nitric oxide, which then diffuses to nearby neurons and modulates synaptic transmission by a postsynaptic mechanism.