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.