Neurotensin-induced Cl- current in guinea-pig dorsal root ganglion cells

In guinea-pig dorsal root ganglion cells held under voltage-clamp at -80 mV , neurotensin elicited an inward current (I-NT) whose amplitude increased w ith increasing neurotensin concentration (40-4000 nM). The effect was block ed by a nonpeptide neurotensin antagonist. I-NT occurred in the absence of the extracellular Na+, but not in the absence of the intracellular Cl-, and it was outward directed by reversing the driving force for Cl-. I-NT, like the gamma-amino-butyric acid (GABA)-induced Cl- current (I-GABA), remained little changed after virtual elimination of cytosolic free-ionized Ca2+ or after treatment with a Ca2+-activated Cl- channel blocker, but, in contras t to I-GABA it was resistant to the I-GABA blocker picrotoxin, slower in ti me course and more easily desensitized when repeatedly elicited. I-NT and I -GABA were additive to each other. AG-protein inhibitor markedly reduced I- NT and a G-protein activator produced an inward current during which no cur rent could be elicited by neurotensin. These results show that neurotensin exerts an effect to activate Ca2+-insensitive Cl- channels distinct from th ose activated by GABA in guinea-pig dorsal root ganglion cells, and the eff ect may arise through a G-protein-dependent mechanism. (C) 2000 Elsevier Sc ience B.V. All rights reserved.