Somatostatin induces an inward rectification in rat locus coeruleus neurones through a pertussis toxin-sensitive mechanism

Abstract

1. Membrane properties and somatostatin effects were studied in cultured locus coeruleus neurones from neonatal rats by using the whole-cell version of the patch clamp technique. 2. The current-voltage relationship of the resting cell revealed an inward-going rectification. The inward currents developed almost instantaneously upon hyperpolarizing the membrane under voltage clamp, and at large negative potentials the inward current showed a time-dependent inactivation. Extracellularly applied Cs+ or Ba2+ (0.1 mM) inhibited the inward current in a voltage-dependent manner. 3. Application of somatostatin (0.01-1 microM) produced an increase in membrane conductance. Somatostatin-induced currents were calculated by subtracting the control current from the current during the somatostatin-induced response. The somatostatin-induced current developed almost instantaneously with hyperpolarization and did not show any time-dependent inactivation. The current-voltage relationship of the somatostatin-induced current exhibited a rectification in the inward direction and showed a reversal potential. The reversal potentials were close to the K+ equilibrium potential. 4. Extracellular Cs+ or Ba2+ (0.1 mM) inhibited the somatostatin-induced currents in a voltage-dependent manner, the effectiveness increasing with hyperpolarization. The somatostatin-induced hyperpolarization was not affected by apamin (20 nM) or by charybdotoxin (100 nM). 5. These results indicate that the somatostatin-induced conductance is very similar to the inward-rectification conductance. Because the somatostatin-induced inward rectification did not exhibit a time-dependent inactivation, this rectification and the inward rectification in the control neurones may arise from two different channels. 6. Pre-treatment of neurones with pertussis toxin abolished the somatostatin-induced response, but did not affect the resting inward rectification. When GTP gamma S was applied intracellularly, somatostatin produced an irreversible activation of the inward rectification conductance. The somatostatin-induced hyperpolarization may therefore be mediated through a pertussis toxin-sensitive GTP-binding protein.