SOMATOSTATIN INCREASES A VOLTAGE-INSENSITIVE K-NEURONS( CONDUCTANCE IN RAT CA1 HIPPOCAMPAL)

Somatostatin (SST) is a neuropeptide involved in several central proce sses. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and aug ments the K+ M current (I-M). However, the Limited involvement of I-M at resting potential in these cells suggests that the peptide also may modulate another channel to hyperpolarize hippocampal pyramidal neuro ns (HPNs). We studied the effect of SST on noninactivating conductance s of rat CA1 HPNs in a slice preparation. Using MK886, a specific inhi bitor of the enzymatic pathway that leads to the augmentation of I-M b y SST, we have uncovered and characterized a second conductance activa ted by the peptide. SST did not affect I-M when applied with MK886 or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-cu rrent 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 an d that displayed a linear current-voltage relationship. Reversal poten tials 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 (I-K(L)) in HPNs not an inwardly rect ifying K+ current as reported in other neuron types. A low concentrati on of extracellular Ba2+ (150 mu M) only slightly decreased the SST-in duced effect in a voltage-independent manner, whereas a high concentra tion of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) di d not affect the outward SST current but inhibited the inward componen t. We conclude that SST inhibits HPNs by activating two different K+ c onductances: the voltage-insensitive I-K(L) and the voltage-dependent I-M. The hyperpolarizing effect of SST at resting membrane potential a ppears to be mainly carried by I-K(L), whereas I-M dominates at slight ly depolarized potentials.