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To assess the actions of thiopental at the spinal dorsal horn level, we examined the effects of thiopental using the whole cell patch-clamp technique on mechanically dissociated rat spinal dorsal horn neurons. Thiopental, at large concentrations, elicited a current (I(Thio)) through activation of chloride conductance, and its threshold concentration was approximately 50 microM. I(Thio) was sensitive to bicuculline, a gamma-aminobutyric acid (GABA)A receptor antagonist, but not to strychnine, a glycine receptor antagonist. At a clinically relevant concentration (30 muM), thiopental markedly enhanced the peak amplitude of a subsaturating GABA-induced current (I(GABA)) but not that of a saturating GABA-induced current. Furthermore, thiopental prolonged the time constants of both desensitization and deactivation of I(GABA). At a large concentration (300 muM), it inhibited the peak amplitude of I(GABA), which may be the result of open-channel blockade. In addition, at 30 microM, thiopental increased the duration and decreased the frequency of GABAergic miniature inhibitory postsynaptic currents. These results indicate that thiopental enhances GABAergic inhibitory transmission and suggest that GABA(A) receptors in the spinal cord are a potential target through which thiopental causes immobility and depresses the response to noxious stimuli.

Aspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid-sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole-cell patch-clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate reduced acidosis-induced membrane depolarization. These data suggest that ASICs in the cortex are molecular targets of high doses of aspirin and salicylate. In addition, the results from lactate dehydrogenase release measurement showed that high doses of aspirin and salicylate protected the cortical neuron from acidosis-induced neuronal injury. These findings may contribute to a better understanding of the therapeutic mechanisms of aspirin and salicylate actions in the brain and provide new evidence on aspirin and salicylate used as neuroprotective agents in the treatment of ischemic stroke.

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