Acknowledgement
This work was supported by grants from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2019R1A2B5B01070546) and the Basic Science Research Program (2020R1A4A1019436).
References
- Harrison NL, Skelly MJ, Grosserode EK et al (2017) Effects of acute alcohol on excitability in the CNS. Neuropharmacology 122, 36-45 https://doi.org/10.1016/j.neuropharm.2017.04.007
- Alderazi Y and Brett F (2007) Alcohol and the nervous system. Curr Diagn Pathol 13, 203-209 https://doi.org/10.1016/j.cdip.2007.04.004
- Hirota Y (1976) Effect of ethanol on contraction and relaxation of isolated rat ventricular muscle. J Mol Cell Cardiol 8, 727-732 https://doi.org/10.1016/0022-2828(76)90014-6
- Harris RA, Trudell JR and Mihic SJ (2008) Ethanol's molecular targets. Sci Signal 1, re7 https://doi.org/10.1126/scisignal.128re7
- Kruse SW, Zhao R, Smith DP and Jones DNM (2003) Structure of a specific alcohol-binding site defined by the odorant binding protein LUSH from Drosophila melanogaster. Nat Struct Mol Biol 10, 694-700 https://doi.org/10.1038/nsb960
- Bodhinathan K and Slesinger PA (2013) Molecular mechanism underlying ethanol activation of G-protein-gated inwardly rectifying potassium channels. Proc Natl Acad Sci U S A 110, 18309-18314 https://doi.org/10.1073/pnas.1311406110
- Koyama S, Brodie MS and Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97, 1977-1985 https://doi.org/10.1152/jn.00270.2006
- Brown DA and Adams PR (1980) Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 283, 673-676 https://doi.org/10.1038/283673a0
- Greene DL and Hoshi N (2017) Modulation of Kv7 channels and excitability in the brain. Cell Mol Life Sci 74, 495-508 https://doi.org/10.1007/s00018-016-2359-y
- Wang H-S, Pan Z, Shi W et al (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282, 1890-1893 https://doi.org/10.1126/science.282.5395.1890
- Telezhkin V, Brown DA and Gibb AJ (2012) Distinct subunit contributions to the activation of M-type potassium channels by PI(4,5)P2. J Gen Physiol 140, 41-53 https://doi.org/10.1085/jgp.201210796
- Suh BC and Hille B (2002) Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis. Neuron 35, 507-520 https://doi.org/10.1016/S0896-6273(02)00790-0
- Falkenburger BH, Jensen JB and Hille B (2010) Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells. J Gen Physiol 135, 99-114 https://doi.org/10.1085/jgp.200910345
- Zhang Q, Zhou P, Chen Z et al (2013) Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating. Proc Natl Acad Sci U S A 110, 20093-20098 https://doi.org/10.1073/pnas.1312483110
- Choveau FS, De la Rosa V, Bierbower SM, Hernandez CC and Shapiro MS (2018) Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates KCNQ3 K+ channels by interacting with four cytoplasmic channel domains. J Biol Chem 293, 19411-19428 https://doi.org/10.1074/jbc.RA118.005401
- Kim KW, Kim K, Lee H and Suh BC (2019) Ethanol elevates excitability of superior cervical ganglion neurons by inhibiting Kv7 channels in a cell type-specific and PI(4,5)P2-dependent manner. Int J Mol Sci 20, 4419 https://doi.org/10.3390/ijms20184419
- Hadley JK, Noda M, Selyanko AA et al (2000) Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br J Pharmacol 129, 413-415 https://doi.org/10.1038/sj.bjp.0703086
- Holmgren M, Smith PL and Yellen G (1997) Trapping of organic blockers by closing of voltage-dependent K+ channels: Evidence for a trap door mechanism of activation gating. J Gen Physiol 109, 527-535 https://doi.org/10.1085/jgp.109.5.527
- Suh BC and Hille B (2007) Electrostatic Interaction of internal Mg2+ with membrane PIP2 seen with KCNQ K+ channels. J Gen Physiol 130, 241-256 https://doi.org/10.1085/jgp.200709821
- Keum D, Kruse M, Kim DI, Hille B and Suh BC (2016) Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence. Proc Natl Acad Sci U S A 113, E3686-E3695 https://doi.org/10.1073/pnas.1606472113
- Jensen JB, Lyssand JS, Hague C and Hille B (2009) Fluorescence changes reveal kinetic steps of muscarinic receptor-mediated modulation of phosphoinositides and Kv7.2/7.3 K+ channels. J Gen Physiol 133, 347-359 https://doi.org/10.1085/jgp.200810075
- Kutluay E, Roux B and Heginbotham L (2005) Rapid intra-cellular TEA block of the KcsA potassium channel. Biophys J 88, 1018-1029 https://doi.org/10.1529/biophysj.104.052043
- Luzhkov VB and Aqvist J (2001) Mechanisms of tetraethylammonium ion block in the KcsA potassium channel. FEBS Lett 495, 191-196 https://doi.org/10.1016/S0014-5793(01)02381-X
- Pegan S, Arrabit C, Slesinger PA and Choe S (2006) Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1. Biochemistry 45, 8599-8606 https://doi.org/10.1021/bi060653d
- Aryal P, Dvir H, Choe S and Slesinger PA (2009) A discrete alcohol pocket involved in GIRK channel activation. Nat Neurosci 12, 988-995 https://doi.org/10.1038/nn.2358
- Covarrubias M, Vyas TB, Escobar L and Wei A (1995) Alcohols inhibit a cloned potassium channel at a discrete saturable site. Insights into the molecular basis of general anesthesia. J Biol Chem 270, 19408-19416 https://doi.org/10.1074/jbc.270.33.19408
- Villarroel A (1997) Nonstationary noise analysis of M currents simulated and recorded in PC12 cells. J Neurophysiol 77, 2131-2138 https://doi.org/10.1152/jn.1997.77.4.2131
- Tatulian L and Brown DA (2003) Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells. J Physiol 549, 57-63 https://doi.org/10.1113/jphysiol.2003.039842
- Schwake M, Pusch M, Kharkovets T and Jentsch TJ (2000) Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J Biol Chem 275, 13343-13348 https://doi.org/10.1074/jbc.275.18.13343
- Selyanko AA, Hadley JK and Brown DA (2001) Properties of single M-type KCNQ2/KCNQ3 potassium channels expressed in mammalian cells. J Physiol 534, 15-24 https://doi.org/10.1111/j.1469-7793.2001.00015.x
- Gao H, Boillat A, Huang D, Liang C, Peers C and Gamper N (2017) Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bis-phosphate. Proc Natl Acad Sci U S A 114, E6410-E6419 https://doi.org/10.1073/pnas.1620598114
- Zhang H, Craciun LC, Mirshahi T et al (2003) PIP2 activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. Neuron 37, 963-975 https://doi.org/10.1016/S0896-6273(03)00125-9
- Keum D, Baek C, Kim DI, Kweon HJ and Suh BC (2014) Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit. J Gen Physiol 144, 297-309 https://doi.org/10.1085/jgp.201411245
- Alvarez O, Gonzalez C and Latorre R (2002) Counting channels: A tutorial guide on ion channel fluctuation analysis. Adv Physio Educ 26, 327-341 https://doi.org/10.1152/advan.00006.2002
- Hartveit E and Veruki ML (2007) Studying properties of neurotransmitter receptors by non-stationary noise analysis of spontaneous postsynaptic currents and agonist-evoked responses in outside-out patches. Nat Protoc 2, 434-448 https://doi.org/10.1038/nprot.2007.47
- Lim NK, Lam AKM and Dutzler R (2016) Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A. J Gen Physiol 148, 375-392 https://doi.org/10.1085/jgp.201611650