2 SIGNAL-TRANSDUCTION MECHANISMS OF SUBSTANCE-P-INDUCED DEPOLARIZATION IN LOCUS-CERULEUS NEURONS

Effects of substance P on cultured neurons of the locus coeruleus of t he rat were studied using the whole-cell patch clamp technique- In som e cells substance P produced a decrease in a K conductance which showe d an inwardly rectifying property. In other cells substance P produced an initial inward current which was accompanied by a conductance incr ease. The rest of the cells showed responses which were mixtures of th e above two responses. The measurement of the reversal potential of th e initial inward current after suppressing the voltage-gated Ca and K conductances suggests that it is caused by an increase in a non-select ive ionic conductance. In cells loaded with 260 muM GTPgammaS, applica tion of substance P produced an irreversible reduction of the K conduc tance, while the initial inward current could still be recorded, sugge sting that the former is mediated by a G protein, whereas the latter m ay be activated by a different signal transduction mechanism. The init ial inward current was not eliminated by external application of high concentrations of tetrodotoxin, d-tubocurarine or amiloride. Nor was i t affected by the intracellular application of cyclic GMP or cyclic AM P.