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.

Aguado, Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. 2008, Pubmed

Aguado, Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. 2008, Pubmed
Altamura, Plasma and brain pharmacokinetics of mianserin after single and multiple dosing in mice. 1987, Pubmed
Bettahi, Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh. 2002, Pubmed
Blednov, Potassium channels as targets for ethanol: studies of G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) null mutant mice. 2001, Pubmed
Bolo, Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. 2000, Pubmed
Bymaster, The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. 2005, Pubmed
Bymaster, Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. 2001, Pubmed
Choi, Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1. 2001, Pubmed
Cruz, Absence and rescue of morphine withdrawal in GIRK/Kir3 knock-out mice. 2008, Pubmed
Cuellar-Quintero, The antidepressant imipramine inhibits the M-type K+ current in rat sympathetic neurons. 2001, Pubmed
Dascal, Signalling via the G protein-activated K+ channels. 1997, Pubmed
Deák, Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. 2000, Pubmed
Dreixler, Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds. 2000, Pubmed
Fan, Effects of antidepressants on the inward current mediated by 5-HT3 receptors in rat nodose ganglion neurones. 1994, Pubmed
Frommer, Tricyclic antidepressant overdose. A review. , Pubmed
Goeringer, Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases. 2000, Pubmed
Gray, The effect of fluvoxamine and sertraline on the opioid withdrawal syndrome: a combined in vivo cerebral microdialysis and behavioural study. 2002, Pubmed
Gulley, Selective serotonin reuptake inhibitors: effects of chronic treatment on ethanol-reinforced behavior in mice. 1995, Pubmed
Harada, [Pharmacological, pharmacokinetic, and clinical profile of sertraline hydrochloride (J ZOLOFT)]. 2006, Pubmed
Hashimoto, Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation. 2006, Pubmed
He, Amoxapine inhibits the delayed rectifier outward K+ current in mouse cortical neurons via cAMP/protein kinase A pathways. 2010, Pubmed
Henry, A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study. 2005, Pubmed
Henry, Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study. 2000, Pubmed
Heurteaux, Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. 2006, Pubmed
Hill, Reduced ethanol-induced conditioned taste aversion and conditioned place preference in GIRK2 null mutant mice. 2003, Pubmed
Holzbach, Suicide attempts with mirtazapine overdose without complications. 1998, Pubmed
Ikeda, Opioid receptor coupling to GIRK channels. In vitro studies using a Xenopus oocyte expression system and in vivo studies on weaver mutant mice. 2003, Pubmed , Xenbase
Inanobe, Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. 1999, Pubmed , Xenbase
Isbister, Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. 2004, Pubmed
Karschin, IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. 1996, Pubmed
Karson, Human brain fluoxetine concentrations. 1993, Pubmed
Kent, SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. 2000, Pubmed
Kobayashi, Inhibition of G protein-activated inwardly rectifying K+ channels by the antidepressant paroxetine. 2006, Pubmed , Xenbase
Kobayashi, Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine. 2010, Pubmed , Xenbase
Kobayashi, Functional characterization of an endogenous Xenopus oocyte adenosine receptor. 2002, Pubmed , Xenbase
Kobayashi, G protein-activated inwardly rectifying potassium channels as potential therapeutic targets. 2006, Pubmed
Kobayashi, Ethanol opens G-protein-activated inwardly rectifying K+ channels. 1999, Pubmed , Xenbase
Kobayashi, Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. 2000, Pubmed , Xenbase
Kobayashi, Inhibition of G protein-activated inwardly rectifying K+ channels by fluoxetine (Prozac). 2003, Pubmed , Xenbase
Kobayashi, Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs. 2004, Pubmed , Xenbase
Kobayashi, Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain. 1995, Pubmed
Kovoor, Agonist-induced desensitization of the mu opioid receptor-coupled potassium channel (GIRK1). 1995, Pubmed , Xenbase
Krapivinsky, The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. 1995, Pubmed , Xenbase
Kubo, Primary structure and functional expression of a mouse inward rectifier potassium channel. 1993, Pubmed , Xenbase
Kubo, Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. 1993, Pubmed , Xenbase
Kuzhikandathil, Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. 2002, Pubmed
Lee, The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones. 1997, Pubmed
Lesage, Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. 1995, Pubmed , Xenbase
Levine, Distribution of venlafaxine in three postmortem cases. 1996, Pubmed
Lewohl, G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. 1999, Pubmed , Xenbase
Liao, Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. 1996, Pubmed
Litovitz, Amoxapine overdose. Seizures and fatalities. 1983, Pubmed
Lobo, In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. 2008, Pubmed
Lüscher, G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. 1997, Pubmed
Lüscher, Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. 2010, Pubmed
Maertens, Block by fluoxetine of volume-regulated anion channels. 1999, Pubmed
Maertens, Block of volume-regulated anion channels by selective serotonin reuptake inhibitors. 2002, Pubmed
Mann, The medical management of depression. 2005, Pubmed
Mathie, Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. 1998, Pubmed
Montgomery, Antidepressants and seizures: emphasis on newer agents and clinical implications. 2005, Pubmed
Morgan, Decreased cocaine self-administration in Kir3 potassium channel subunit knockout mice. 2003, Pubmed
Musshoff, Fatal blood and tissue concentrations of more than 200 drugs. 2004, Pubmed
Nacca, Brain-to-blood partition and in vivo inhibition of 5-hydroxytryptamine reuptake and quipazine-mediated behaviour of nefazodone and its main active metabolites in rodents. 1998, Pubmed
Nakazawa, Block and unblock by imipramine of cloned and mutated P2X2 receptor/channel expressed in Xenopus oocytes. 1999, Pubmed , Xenbase
Ni, Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac). 1997, Pubmed , Xenbase
North, Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells. 1989, Pubmed
Ogata, Psychotropic drugs block voltage-gated ion channels in neuroblastoma cells. 1989, Pubmed
Pabon, Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function. 2000, Pubmed
Pancrazio, Inhibition of neuronal Na+ channels by antidepressant drugs. 1998, Pubmed
Pettinati, Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. 2000, Pubmed
Reimann, Inwardly rectifying potassium channels. 1999, Pubmed
Schatzberg, New indications for antidepressants. 2000, Pubmed
Scherer, Inhibition of cardiac hERG potassium channels by tetracyclic antidepressant mianserin. 2008, Pubmed , Xenbase
Sedgwick, Toxicological findings in amoxapine overdose. 1982, Pubmed
Sernagor, Open channel block of NMDA receptor responses evoked by tricyclic antidepressants. 1989, Pubmed
Shytle, Nicotinic acetylcholine receptors as targets for antidepressants. 2002, Pubmed
Sigel, Use of Xenopus oocytes for the functional expression of plasma membrane proteins. 1990, Pubmed , Xenbase
Signorini, Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2. 1997, Pubmed
Stahl, SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. 2005, Pubmed
Sánchez, Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike? 1997, Pubmed
Taylor, The determination of amoxapine in human fatal overdoses. 1982, Pubmed
Terstappen, Pharmacological characterisation of the human small conductance calcium-activated potassium channel hSK3 reveals sensitivity to tricyclic antidepressants and antipsychotic phenothiazines. 2001, Pubmed
Teschemacher, Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. 1999, Pubmed
Tremaine, Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog. 1989, Pubmed
Uhr, Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. 2003, Pubmed
Vey, Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey. 2010, Pubmed
Whyte, Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. 2003, Pubmed