Postsynaptic action mechanism of somatostatin on the membrane excitability in spinal substantia gelatinosa neurons of juvenile rats.

We used tight-seal, whole-cell recording in juvenile rat spinal slices to investigate the action of somatostatin on substantia gelatinosa neurons. Bath application of somatostatin caused a robust and repeatable hyperpolarization or outward current in substantia gelatinosa neurons. Somatostatin inhibited spontaneous action potentials in subpopulation of substantia gelatinosa neurons. The amplitude of dorsal root-evoked excitatory postsynaptic currents and the frequency of spontaneous excitatory postsynaptic currents were not affected by somatostatin. The current induced by somatostatin developed almost instantaneously and did not show any time-dependent inactivation. The current-voltage relationship exhibited inward rectification. The conductance of somatostatin-sensitive current increased with the concentration of external K(+). The reversal potentials in different external K(+) concentrations were close to the K(+) equilibrium potentials. The effect of somatostatin was dose-dependent, with an EC(50) of 113 nM. The somatostatin-sensitive current was blocked by low concentration of extracellular Ba(2+) but not by glibenclamide, an inhibitor of ATP-sensitive K(+) channels. Hyperpolarization-activated cation current in a subpopulation of substantia gelatinosa neurons was not affected by somatostatin. In neurons recorded with an internal solution containing GTPgammaS, somatostatin induced outward current and hyperpolarization that did not reverse on washing. When the spontaneous induction of outward current with GTPgammaS was greatest, somatostatin did not induce any outward currents. Furthermore, intracellular dialysis of GDPbetaS, a G-protein antagonist, abolished the effect of somatostatin. In addition, SST-sensitive neurons were fewer in slices incubated with pertussis toxin than in adjacent control slices incubated without pertussis toxin. These results suggest that somatostatin decreases the postsynaptic membrane excitability of substantia gelatinosa neurons by a pertussis toxin-sensitive G-protein-mediated activation of an inwardly rectifying K(+) conductance.