Modulation of membrane K+ conductance in T-lymphocytes by substance P via a GTP-binding protein.
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 200 nM 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.
Schumann
M A
MA
Department of Medicine, Stanford University, California.
Gardner
P
P
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D013373:Substance P; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium