Abstract
The mechanism by which substance P depolarizes cholinergic interneurons in the rat striatum was studied using whole-cell recording techniques. In all cases the effects of substance P were mimicked by the neurokinin 1 receptor agonist [Sar 9, Met(O 2) 11] substance P and were antagonized by the neurokinin 1 receptor antagonist SR140333. [Sar 9, Met(O 2) 11] substance P was found to depolarize cholinergic interneurons by the induction of a calcium-activated inward current at −60 mV. This inward current was irreversibly potentiated by photolysis of caged GTP γS within neurons implicating the involvement of a G-protein. The [Sar 9, Met(O 2) 11] substance P-induced inward current was inhibited by the phospholipase C inhibitor U-73122, and by the inclusion of the inositol-1,4,5-triphosphate receptor antagonist heparin in the electrode solution. These findings suggest that neurokinin 1 receptors depolarize cholinergic interneurons in the rat striatum primarily through a phosphoinositide signalling pathway.
Published Version
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