SOMATOSTATIN INCREASES A VOLTAGE-INSENSITIVE K+ CONDUCTANCE IN RAT CA1 HIPPOCAMPAL NEURONS. Paul Schweitzer, Samuel G. Madamba, and George R. Siggins. The Scripps Research Institute, Department of Neuropharmacology, CVN 12, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
APStracts 4:342N, 1997.
ABSTRACT
Somatostatin (SST) is a neuropeptide involved in several central processes. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and augments the K+ M- current (IM). However, the limited involvement of IM at resting potential in these cells suggests that the peptide may also modulate another channel to hyperpolarize HPNs. We studied the effect of SST on non-inacti~ vating conductances of rat CA1 hippocampal pyramidal neurons (HPNs) in a slice preparation. Using MK886, a specific inhibitor of the enzymatic pathway that leads to the augmentation of IM by SST, we have uncovered and characterized a second conductance activated by the peptide. SST did not affect IM when applied with MK886, or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-current and the cationic Q-current, but still caused an outward current, indicating that SST acts upon another conductance. In the presence of MK886, SST elicited an outward current that reversed around -100 mV and that displayed a linear current-voltage rela~ tionship. Reversal potentials obtained in different external K+ concentrations are consistent with a conductance carried solely by K+ ions. The slope of the current-voltage relationship increased proportionately with the extracellular K+ concentration and remained linear. This suggests that SST opens a voltage-insensitive leak current (IK(L)) in HPNs, not an inwardly rectifying K+ current as reported in other neuron types. A low concentration of extracellular Ba2+ (150 mM) only slightly decreased the SST-induced effect in a voltage-independent manner, whereas a high concentration of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) did not affect the outward SST current but inhibited the inward component. We conclude that SST inhibits HPNs by activating two different K+ conductances: the voltage-insensitive IK(L) and the voltage- dependent IM. The hyperpolarizing effect of SST at resting membrane potential appears to be mainly carried by IK(L), whereas IM dominates at slightly depolarized potentials. 

Received 28 August 1997; accepted in final form 26 November 1997.
APS Manuscript Number J716-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997