Kobayashi T , Washiyama K , Ikeda K .

	Figure 1. Inhibitory effects of sertraline on GIRK channels expressed in Xenopus oocytes.(A) In an oocyte injected with GIRK1 and GIRK2 mRNAs, current responses to 30 µM sertraline and 3 mM Ba2+ are shown. (B) In an oocyte injected with Kir2.1 mRNA, current responses to 100 µM sertraline and 3 mM Ba2+ are shown. (C) In an uninjected oocyte, no significant current responses to 300 µM sertraline or 3 mM Ba2+ are shown. Current responses were measured at a membrane potential of −70 mV in an hK solution that contained 96 mM K+. Asterisks show the zero current level. Horizontal bars indicate the duration of application.
	Figure 2. Concentration-response relationships for the effects of various antidepressants on GIRK1/2 and GIRK1/4 channels.The magnitudes of inhibition of GIRK currents by the drugs were compared with the 3 mM Ba2+-sensitive current components in oocytes that expressed GIRK1/2 channels or GIRK1/4 channels (762.8±36.0 nA, n = 50, and 585.0±44.0 nA, n = 40, respectively). Each point and error bar represent the mean ± SEM of the percentage responses.
	Figure 3. Characteristics of the inhibitory effects of sertraline and duloxetine on GIRK currents.(A) Representative GIRK1/2 currents elicited by a voltage step to −100 mV for 2 s from a holding potential of 0 mV in the presence or absence of 30 µM sertraline (left) or 30 µM duloxetine (right) applied for 3 min. Current responses were recorded in an hK solution that contained 96 mM K+. Arrows indicate the zero current level. (B) Current-voltage relationships of the magnitudes of 3 mM Ba2+-sensitive currents and the magnitudes of currents reduced by 30 µM sertraline (left, n = 9) or 30 µM duloxetine (right, n = 6) in oocytes that expressed GIRK1/2 channels. Current responses were normalized to the 3 mM Ba2+-sensitive current component measured at a membrane potential of −100 mV (1851.0±220.4 nA, n = 15). (C) Percentage inhibition of GIRK1/2 channels by 30 µM sertraline or 30 µM duloxetine over the voltage range of −120 to −40 mV. The magnitudes of inhibition of GIRK currents by 30 µM sertraline (left, n = 9) and duloxetine (right, n = 6) at the end of the voltage pulses were compared with the 3 mM Ba2+-sensitive current components. All values are expressed as mean ± SEM.
	Figure 4. Concentration-dependent inhibition of GIRK channels by sertraline or duloxetine at different pH values.The magnitudes of inhibition of GIRK currents by the antidepressants were compared with the 3 mM Ba2+-sensitive current components in oocytes that expressed GIRK1/2 channels (1020.8±96.2 nA at pH 7.4, n = 16 for sertraline and n = 7 for duloxetine; 1079.5±173.8 nA at pH 9.0, n = 7 for sertraline and n = 6 for duloxetine, respectively). Current responses were measured at a membrane potential of −70 mV in an hK solution that contained 96 mM K+. Each point and error bar represent the mean ± SEM of the percentage responses.
	Figure 5. Effects of sertraline on total GIRK currents composed of GTPγS-induced and basal GIRK currents.For comparison, the effects on GTPγS-untreated basal GIRK currents shown in Figure 2 are also shown. The magnitudes of inhibition of GIRK currents by sertraline were compared with the 3 mM Ba2+-sensitive current components. Each point and error bar represent the mean ± SEM of the percentage responses (n = 5 for GTPγS-injected oocytes and n = 16 for GTPγS-untreated oocytes). Current responses were measured at a membrane potential of −70 mV in an hK solution that contained 96 mM K+.
	Figure 6. Effect of sertraline on ethanol-induced GIRK currents.(A) Current responses to 100 mM ethanol (EtOH), 100 mM EtOH in the presence of 30 µM sertraline, and 100 mM EtOH in an oocyte injected with GIRK1 and GIRK2 mRNAs. Asterisk indicates the zero current level. Bars show the duration of application. (B) Concentration-dependent inhibition of EtOH-induced GIRK currents by sertraline. Icontrol is the amplitude of GIRK currents induced by 100 mM EtOH (344.2±40.3 nA, n = 6), and I is the current amplitude in the presence of sertraline. (C) Lack of effect of intracellular sertraline on 100 mM EtOH-induced GIRK currents. The amplitude of EtOH-induced GIRK currents after sertraline injection (black bar) was compared with EtOH-induced GIRK currents before the injection (control, white bar) in the same oocyte that expressed GIRK channels (n = 5). Current responses were measured at a membrane potential of −70 mV in an hK solution that contained 96 mM K+. All values are expressed as mean ± SEM.

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