CARBACHOL INDUCES INWARD CURRENT IN RAT NEOSTRIATAL NEURONS THROUGH AG-PROTEIN-COUPLED MECHANISM

Our recent study demonstrated that carbachol can act at M(1)-like musc arinic receptors to reduce the membrane K+ conductance and excite the neostriatal neurons. In the present study, we further studied the mole cular mechanism by which carbachol induced inward currents in neostria tal neurons. In acutely isolated neostriatal neurons held at -60 mV, p ressure application of carbachol (30 mu M) induced a transient inward current underlying whole-cell voltage-clamp mode. In cells loaded with the stable GDP analogue guanosine 5'-0-(2-thiodiphosphate) (GDP-beta- S, 1 mM), the carbachol-induced inward current was significantly dimin ished. However, the carbachol response was not affected by intracellul ar dialysis of the neostriatal neurons with either protein kinase C (P KC) inhibitors, PKCI 19-36 (5 mu M) or NPC-15437 (20 mu M), or a poten t cAMP-dependent protein kinase (PKA) inhibitor, Rp-cAMPS (25 mu M). T hese results show that a G-protein-coupled mechanism mediates carbacho l-induced inward current in the neostriatal neurons and that neither P KC- nor PKA-dependent intracellular transduction pathways are involved in the carbachol response. (C) 1997 Elsevier Science Ireland Ltd.