NPY activates a GIRK current in hypocretin neurons. A, Representative traces showing the currents elicited by 600 msec voltage ramps from -140 to -20 mV before, during, and after the application of NPY (1 μm) in a typical hypocretin cell. High (16 mm) extracellular potassium was used in this experiment. B, Net currents were obtained by subtracting control from NPY currents. Here, the NPY-induced currents in normal (3 mm) and high (16 mm) extracellular potassium are shown. The reversal potential was -90.9 ± 1.6 mV (n = 14) and -50.7 ± 2.1 mV (n = 8) in normal and high extracellular potassium, respectively. C, The NPY-induced current was completely blocked by barium (1 mm) in the bath. D, The NPY-induced current is attenuated after a 5 min intracellular dialysis of GDP-βS, but not after a short 1 min interval. E, The Y1 receptor subtype agonist [Pro³⁴]-NPY (1 μm) also induced a robust inward rectifier current. This current reversed at -51.5 ± 2.5 mV (extracellular K⁺, 16 mm; n = 4) and was blocked by external barium (1 mm). F, The NPY-induced current was blocked with BIBP3226 (1 μm).