Figure 4. Pyruvate suppression of glucose response is reversed by oligomycin and mimicked by intracellular ATP.

A, representative membrane potential response of an orexin cell to 1→5 mm switch in glucose in the presence of 5 mm pyruvate and 2 μm oligomycin (similar responses were observed in 5 cells).B, net currents induced by 1→5 mm glucose in 5 mm pyruvate (grey), and 5 mm pyruvate + 2 μm oligomycin. Each trace shows mean current (5 cells in each group). Repeated measures ANOVA showed that there is a significant difference between the two datasets (F_(1,56) = 39.6, ***P< 0.001). Current at –40 mV was significantly greater in the presence of oligomycin (P< 0.01 by unpairedttest).C, representative membrane potential response of an orexin cell to 1→5 mm switch in glucose in the presence of 20 mm intracellular ATP (similar responses were observed in 5 cells).D, dose–response of ATP-induced inhibition of the current (at –40 mV) induced by 1→5 mm switch in extracellular glucose (n = 4–7 cells per point, IC₅₀ = 11.44 mm, fit details are given in Methods).