Abstract
Recent studies have implicated that spinal GIRK channels play an important role in thermal nociception and the analgesic action of morphine or other related agents. In this study, we have shown that spinal GIRK channels are activated by an endogenous neurotransmitter using whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurons 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 SG neurons recorded. The slow IPSCs increased in amplitude and duration with increasing number of the stimuli and significantly decreased by the removal of Ca2+ from external Krebs solution. The slow IPSC was associated with an increase in membrane conductance and reversed its polarity at a potential close to the equilibrium potential for K+, calculated from the Nernst equation. The slow IPSC was blocked by the addition of GDP-b-S into patch-pipette solution, reduced in amplitude in the presence of Ba2+, and significantly suppressed in the presence of tertiapin-Q, a selective antagonist for GIRK channels. Moreover, somatostatin produced an outward current in a subpopulation of SG neurons and the slow IPSC was occluded during the somatostatin-induced outward current. These results suggest that endogenously-released somatostatin may induce slow IPSCs through the activation of GIRK channels in SG neurons. [J Physiol Sci. 2008;58 Suppl:S175]
