Recent studies have suggested that spinal G-protein-coupled, inwardly rectifying K+ (GIRK) channels play an important role in thermal nociception and the analgesic actions of morphine and other agents. In this study, we show that spinal GIRK channels are activated by an endogenous neurotransmitter using whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurones in adult rat spinal cord slices. Although repetitive stimuli applied to the dorsal root did not induce any slow responses, ones focally applied to the spinal dorsal horn produced slow inhibitory postsynaptic currents (IPSCs) at a holding potential of -50 mV in about 30% of the SG neurones recorded. The amplitude and duration of slow IPSCs increased with the number of stimuli and decreased with removal of Ca2+ from the external Krebs solution. Slow IPSCs were associated with an increase in membrane conductance; their polarity was reversed at a potential close to the equilibrium potential for K+, calculated from the Nernst equation. Slow IPSCs were blocked by addition of GDP-β-S into the patch-pipette solution, reduced in amplitude in the presence of Ba2+, and significantly suppressed in the presence of an antagonist of GIRK channels, tertiapin-Q. Somatostatin produced an outward current in a subpopulation of SG neurones and the slow IPSC was occluded during the somatostatin-induced outward current. Moreover, slow IPSCs were significantly inhibited by the somatostatin receptor antagonist cyclo-somatostatin. These results suggest that endogenously released somatostatin may induce slow IPSCs through the activation of GIRK channels in SG neurones; this slow synaptic transmission might play an important role in spinal antinociception.
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