Modulation of membrane K+ conductance in T-lymphocytes by substance P via a GTP-binding protein

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Abstract
Summary Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. Whole-cell recordings from Jurkat E6-1 human T-lymphocytes revealed two components of substance P action on the outward K+ current: (i) dose- and time-dependent reduction of current peak amplitude; and (ii) acceleration of the current inactivation rate. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist, [d-Arg1,d-Phe5,d-Trp7.9, Leu11]-substance P. As indicated by conductance-voltage relationship, the reduction in current peak amplitude as a result of substance P application was not due to a shift of the voltage dependence of the channel. Raising intracellular free calcium concentration from 2 to 200nm reversed the reduction, induced by substance P, in current peak amplitude and disclosed an apparent desensitization towards the neuropeptide action. The treatment, however, did not reverse substance P-induced acceleration of the rate of current decay. Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP—binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. The data demonstrate a modulation of T-lymphocyte K+ channels by substance P and substantiate a possible role for GTP-binding proteins in this modulation.