Fig. 5. Anandamide blocks IKso in cerebellum granule neurons. (A) Identification of IKso in cultured cerebellar granule neurons. Currents are recorded in the perforated patch configuration with voltage ramps of 600 ms duration, applied from a holding potential of 0 mV. IKso is inhibited at pH 6.4 and stimulated by 740 µM halothane. In a symmetrical K+ gradient, the I–V relationship is linear and reverses at 0 mV. (B) Time course of the effects of external acidosis and halothane on IKso recorded at ∼0 mV. The inset shows that external acidosis to pH 6.4 reduces the steady outward current recorded at 0 mV, but fails to affect the current recorded at –80 mV. (C) Effects of 10 µM methanandamide (met) and external acidosis to pH 6.4 on IKso recorded during a voltage ramp from 50 to –120 mV. The holding potential is 0 mV. The time course of the experiment (monitored at 50 mV) is illustrated in the inset. (D) Effects of 10 µM methanandamide (met) on IKso in the absence and in the presence of 3 µM CB1 receptor antagonist SR141716A. The addition of 10 µM arachidonic acid fails to affect IKso. IKso is recorded at 0 mV.