LY379268 exerts an inhibitory effect on IPSP recorded from cholinergic interneurons. A, A control IPSP evoked by intrastriatal stimulation in MK-801, CNQX, and BMI (30, 10, and 10 μm, respectively) in the perfusing solution was significantly reduced in amplitude by LY379268 (5 min, 10 μm) in a reversible manner. B, A dose–response curve for the inhibitory effect of LY379268 revealed an IC50 of 1.6 ± 0.5 μm. Each data point was obtained by averaging at least four independent observations. C, The P-type HVA channel blocker ω-Aga-IVA (20 nm) significantly reduced the IPSP amplitude recorded in 30 μm MK-801, 10 μmCNQX, and 10 μm BMI. After reaching a steady-state inhibition with ω-Aga-IVA, coapplication of ω-Aga-IVA plus LY379268 (10 μm) did not induce any further decrease in IPSP amplitude. D, ω-Ctx-GVIA (1 μm) reduced the IPSP amplitude. The following bath application of LY379268 (10 μm) produced an additional decrease in the IPSP amplitude. E, Bath application of oxotremorine (300 nm, 1 min) hyperpolarized the recorded cell and blocked the action potential discharge in a reversible manner. In LY379268 (10 μm, 10 min preincubation), the oxotremorine-mediated effect was not modified.
