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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 郭鐘金 | |
dc.contributor.author | Chiung-Wei Huang | en |
dc.contributor.author | 黃烱瑋 | zh_TW |
dc.date.accessioned | 2021-06-16T08:32:18Z | - |
dc.date.available | 2019-02-25 | |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-12-16 | |
dc.identifier.citation | Armstrong CM. (1969). Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J Gen Physiol 54, 553-575.
Berendsen HJC, Postma, J.P.M., Vangunsteren, W.F., Dinola, A., Haak, J.R. (1984). Molecular-dynamics with coupling to an external bath. J Chem Phys 81, 3684-3690. Bichet D, Haass FA & Jan LY. (2003). Merging functional studies with structures of inward-rectifier K(+) channels. Nat Rev Neurosci 4, 957-967. Carr DB & Surmeier DJ. (2007). M1 muscarinic receptor modulation of Kir2 channels enhances temporal summation of excitatory synaptic potentials in prefrontal cortex pyramidal neurons. J Neurophysiol 97, 3432-3438. Chakraborty AT & Youssef I. (2009). Successful treatment of intractable post-ictal psychosis with adjunctive ethosuximide. Seizure 18, 84. Chang HK & Shieh RC. (2003). Conformational changes in Kir 2.1 channels during NH4+-induced inactivation. J Biol Chem 278, 908-918. Chang HK, Yeh SH & Shieh RC. (2003). The effects of spermine on the accessibility of residues in the M2 segment of Kir 2.1 channels expressed in Xenopus oocytes. J Physiol 553, 101-112. Chang HK, Yeh SH & Shieh RC. (2005). A ring of negative charges in the intracellular vestibule of Kir 2.1 channel modulates K+ permeation. Biophys J 88, 243-254. Chang HK, Yeh SH & Shieh RC. (2007). Charges in the cytoplasmic pore control intrinsic inward rectification and single-channel properties in Kir1.1 and Kir 2.1 channels. J Membr Biol 215, 181-193. Chang HR & Kuo CC. (2007). Extracellular proton-modulated pore-blocking effect of the anticonvulsant felbamate on NMDA channels. Biophys J 93, 1981-1992. Chang HR & Kuo CC. (2008). The activation gate and gating mechanism of the NMDA receptor. J Neurosci 28, 1546-1556. Cheong E & Shin HS. (2013). T-type Ca(2)(+) channels in absence epilepsy. Biochim Biophys Acta 1828, 1560-1571. Choi KL, Mossman C, Aube J & Yellen G. (1993). The internal quaternary ammonium receptor site of Shaker potassium channels. Neuron 10, 533-541. Clarke OB, Caputo AT, Hill AP, Vandenberg JI, Smith BJ & Gulbis JM. (2010). Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels. Cell 141, 1018-1029. Coulter DA, Huguenard JR & Prince DA. (1989). Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons. Neurosci Lett 98, 74-78. Crunelli V & Leresche N. (2002a). Block of Thalamic T-Type Ca(2+) Channels by Ethosuximide Is Not the Whole Story. Epilepsy Curr 2, 53-56. Crunelli V & Leresche N. (2002b). Childhood absence epilepsy: genes, channels, neurons and networks. Nat Rev Neurosci 3, 371-382. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT & MacKinnon R. (1998). The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69-77. Drummond GB. (2009). Reporting ethical matters in the Journal of Physiology: standards and advice. J Physiol 587, 713-719. Fakler B, Brandle U, Bond C, Glowatzki E, Konig C, Adelman JP, Zenner HP & Ruppersberg JP. (1994). A structural determinant of differential sensitivity of cloned inward rectifier K+ channels to intracellular spermine. FEBS Lett 356, 199-203. Fakler B, Brandle U, Glowatzki E, Weidemann S, Zenner HP & Ruppersberg JP. (1995). Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine. Cell 80, 149-154. Ficker E, Taglialatela M, Wible BA, Henley CM & Brown AM. (1994). Spermine and spermidine as gating molecules for inward rectifier K+ channels. Science 266, 1068-1072. Fletcher GH & Chiappinelli VA. (1992). An inward rectifier is present in presynaptic nerve terminals in the chick ciliary ganglion. Brain Res 575, 103-112. Fujiwara Y & Kubo Y. (2002). Ser165 in the second transmembrane region of the Kir 2.1 channel determines its susceptibility to blockade by intracellular Mg2+. J Gen Physiol 120, 677-693. Fujiwara Y & Kubo Y. (2006). Functional roles of charged amino acid residues on the wall of the cytoplasmic pore of Kir 2.1. J Gen Physiol 127, 401-419. Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO & Adamson PC. (2013). Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia 54, 141-155. Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Capparelli EV & Adamson PC. (2010). Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 362, 790-799. Goren MZ & Onat F. (2007). Ethosuximide: from bench to bedside. CNS Drug Rev 13, 224-239. Gorji A, Mittag C, Shahabi P, Seidenbecher T & Pape HC. (2011). Seizure-related activity of intralaminar thalamic neurons in a genetic model of absence epilepsy. Neurobiology of disease 43, 266-274. Greger R. (1990). An electrophysiological approach to the study of isolated perfused tubules. Methods Enzymol 191, 289-302. Guo D & Lu Z. (2003). Interaction mechanisms between polyamines and IRK1 inward rectifier K+ channels. J Gen Physiol 122, 485-500. Hagiwara S, Miyazaki S & Rosenthal NP. (1976). Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish. J Gen Physiol 67, 621-638. Hagiwara S & Takahashi K. (1974a). The anomalous rectification and cation selectivity of the membrane of a starfish egg cell. J Membr Biol 18, 61-80. Hagiwara S & Takahashi K. (1974b). Mechanism of anion permeation through the muscle fibre membrane of an elasmobranch fish, Taeniura lymma. J Physiol 238, 109-127. Hansen SB, Olsen SI & Ujang Z. (2012). Greenhouse gas reductions through enhanced use of residues in the life cycle of Malaysian palm oil derived biodiesel. Bioresour Technol 104, 358-366. Hansen SB, Tao X & MacKinnon R. (2011). Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2. Nature 477, 495-498. Hartmann HA, Kirsch GE, Drewe JA, Taglialatela M, Joho RH & Brown AM. (1991). Exchange of conduction pathways between two related K+ channels. Science 251, 942-944. Hattersley AT & Ashcroft FM. (2005). Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 54, 2503-2513. Heginbotham L, Kolmakova-Partensky L & Miller C. (1998). Functional reconstitution of a prokaryotic K+ channel. J Gen Physiol 111, 741-749. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I & Kurachi Y. (2010). Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90, 291-366. Hille B. (2001). Ionic channels of excitable membrane. Sinauer assoc, Sunerland MA. Hille B & Schwarz W. (1978). Potassium channels as multi-ion single-file pores. J Gen Physiol 72, 409-442. Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV & Hebert SC. (1993). Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature 362, 31-38. Hodgkin AL & Horowicz P. (1959). The influence of potassium and chloride ions on the membrane potential of single muscle fibres. J Physiol 148, 127-160. Hodgkin AL & Keynes RD. (1955). The potassium permeability of a giant nerve fibre. J Physiol 128, 61-88. Holmgren M, Smith PL & 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. Howe MW, Feig SL, Osting SM & Haberly LB. (2008). Cellular and subcellular localization of Kir 2.1 subunits in neurons and glia in piriform cortex with implications for K+ spatial buffering. J Comp Neurol 506, 877-893. Huang CW & Kuo CC. (2013). The bundle crossing region is responsible for the inwardly rectifying internal spermine block of the Kir 2.1 channel. Pflugers Arch. Huang PT, Chen TY, Tseng LJ, Lou KL, Liou HH, Lin TB, Spatz HC & Shiau YY. (2002). Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1. Receptors Channels 8, 79-85. Huguenard JR & Prince DA. (1994). Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust antioscillatory effects. J Neurosci 14, 5485-5502. Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J & Seino S. (1996). A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16, 1011-1017. Inagaki N, Gonoi T, Clement JPt, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S & Bryan J. (1995). Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270, 1166-1170. Inanobe A, Nakagawa A & Kurachi Y. (2011). Interactions of cations with the cytoplasmic pores of inward rectifier K(+) channels in the closed state. J Biol Chem 286, 41801-41811. Ishihara K & Ehara T. (2004). Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir 2.1 channel expressed in a human cell line. J Physiol 556, 61-78. Ishihara K & Yan DH. (2007). Low-affinity spermine block mediating outward currents through Kir 2.1 and Kir2.2 inward rectifier potassium channels. J Physiol 583, 891-908. Ishihara K, Yan DH, Yamamoto S & Ehara T. (2002). Inward rectifier K(+) current under physiological cytoplasmic conditions in guinea-pig cardiac ventricular cells. J Physiol 540, 831-841. Ishikawa T, Wegman EA & Cook DI. (1993). An inwardly rectifying potassium channel in the basolateral membrane of sheep parotid secretory cells. J Membr Biol 131, 193-202. Iwasaki N, Kawamura M, Yamagata K, Cox NJ, Karibe S, Ohgawara H, Inagaki N, Seino S, Bell GI & Omori Y. (1996). Identification of microsatellite markers near the human genes encoding the beta-cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese. Diabetes 45, 267-269. Jiang Y, Lee A, Chen J, Cadene M, Chait BT & MacKinnon R. (2002). The open pore conformation of potassium channels. Nature 417, 523-526. Karschin C, Dissmann E, Stuhmer W & Karschin A. (1996). IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J Neurosci 16, 3559-3570. Katz B. (1949). The efferent regulation of the muscle spindle in the frog. J Exp Biol 26, 201-217. Khurana A, Shao ES, Kim RY, Vilin YY, Huang X, Yang R & Kurata HT. (2011). Forced gating motions by a substituted titratable side chain at the bundle crossing of a potassium channel. J Biol Chem 286, 36686-36693. Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW & Shin HS. (2001). Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels. Neuron 31, 35-45. Kitaguchi T, Sukhareva M & Swartz KJ. (2004). Stabilizing the closed S6 gate in the Shaker Kv channel through modification of a hydrophobic seal. J Gen Physiol 124, 319-332. Kostyuk PG, Molokanova EA, Pronchuk NF, Savchenko AN & Verkhratsky AN. (1992). Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons. Neuroscience 51, 755-758. Kubo Y, Baldwin TJ, Jan YN & Jan LY. (1993a). Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362, 127-133. Kubo Y & Murata Y. (2001). Control of rectification and permeation by two distinct sites after the second transmembrane region in Kir 2.1 K+ channel. J Physiol 531, 645-660. Kubo Y, Reuveny E, Slesinger PA, Jan YN & Jan LY. (1993b). Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. Nature 364, 802-806. Kubo Y, Yoshimichi M & Heinemann SH. (1998). Probing pore topology and conformational changes of Kir 2.1 potassium channels by cysteine scanning mutagenesis. FEBS Lett 435, 69-73. Kuffler SW & Nicholls JG. (1966). The physiology of neuroglial cells. Ergeb Physiol 57, 1-90. Kuo A, Gulbis JM, Antcliff JF, Rahman T, Lowe ED, Zimmer J, Cuthbertson J, Ashcroft FM, Ezaki T & Doyle DA. (2003). Crystal structure of the potassium channel KirBac1.1 in the closed state. Science 300, 1922-1926. Kuo CC & Hess P. (1993). Block of the L-type Ca2+ channel pore by external and internal Mg2+ in rat phaeochromocytoma cells. J Physiol 466, 683-706. Kuo CC & Yang S. (2001). Recovery from inactivation of t-type ca2+ channels in rat thalamic neurons. J Neurosci 21, 1884-1892. Kurachi Y. (1995). G protein regulation of cardiac muscarinic potassium channel. Am J Physiol 269, C821-830. Kurata HT, Akrouh A, Li JB, Marton LJ & Nichols CG. (2013). Scanning the topography of polyamine blocker binding in an inwardly-rectifying potassium channel. J Biol Chem. Kurata HT, Cheng WW, Arrabit C, Slesinger PA & Nichols CG. (2007). The role of the cytoplasmic pore in inward rectification of Kir 2.1 channels. J Gen Physiol 130, 145-155. Kurata HT, Diraviyam K, Marton LJ & Nichols CG. (2008). Blocker protection by short spermine analogs: refined mapping of the spermine binding site in a Kir channel. Biophys J 95, 3827-3839. Kurata HT & Fedida D. (2006). A structural interpretation of voltage-gated potassium channel inactivation. Prog Biophys Mol Biol 92, 185-208. Kurata HT, Marton LJ & Nichols CG. (2006). The polyamine binding site in inward rectifier K+ channels. J Gen Physiol 127, 467-480. Kurata HT, Phillips LR, Rose T, Loussouarn G, Herlitze S, Fritzenschaft H, Enkvetchakul D, Nichols CG & Baukrowitz T. (2004). Molecular basis of inward rectification: polyamine interaction sites located by combined channel and ligand mutagenesis. J Gen Physiol 124, 541-554. Kurata HT, Zhu EA & Nichols CG. (2010). Locale and chemistry of spermine binding in the archetypal inward rectifier Kir 2.1. J Gen Physiol 135, 495-508. Leresche N, Parri HR, Erdemli G, Guyon A, Turner JP, Williams SR, Asprodini E & Crunelli V. (1998). On the action of the anti-absence drug ethosuximide in the rat and cat thalamus. J Neurosci 18, 4842-4853. Levitt DG & Subramanian G. (1974). A new theory of transport for cell membrane pores. II. Exact results and computer simulation (molecular dynamics). Biochim Biophys Acta 373, 132-140. Li-Smerin Y & Swartz KJ. (1998). Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. Proc Natl Acad Sci U S A 95, 8585-8589. Liu TA, Chang HK & Shieh RC. (2012). Revisiting inward rectification: K ions permeate through Kir 2.1 channels during high-affinity block by spermidine. J Gen Physiol 139, 245-259. Lopatin AN, Makhina EN & Nichols CG. (1994). Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature 372, 366-369. Lopatin AN, Makhina EN & Nichols CG. (1995). The mechanism of inward rectification of potassium channels: 'long-pore plugging' by cytoplasmic polyamines. J Gen Physiol 106, 923-955. Lopatin AN & Nichols CG. (1996). [K+] dependence of polyamine-induced rectification in inward rectifier potassium channels (IRK1, Kir 2.1). J Gen Physiol 108, 105-113. Lopes CM, Remon JI, Matavel A, Sui JL, Keselman I, Medei E, Shen Y, Rosenhouse-Dantsker A, Rohacs T & Logothetis DE. (2007). Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels. Channels (Austin) 1, 124-134. Lou KL, Huang PT, Shiau YS, Liaw YC, Shiau YY & Liou HH. (2003). A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+-channels. J Mol Recognit 16, 392-395. Loussouarn G, Rose T & Nichols CG. (2002). Structural basis of inward rectifying potassium channel gating. Trends Cardiovasc Med 12, 253-258. Lu T, Nguyen B, Zhang X & Yang J. (1999). Architecture of a K+ channel inner pore revealed by stoichiometric covalent modification. Neuron 22, 571-580. Lu Z. (2004). Mechanism of rectification in inward-rectifier K+ channels. Annu Rev Physiol 66, 103-129. Lu Z, Klem AM & Ramu Y. (2001). Ion conduction pore is conserved among potassium channels. Nature 413, 809-813. Lu Z, Klem AM & Ramu Y. (2002). Coupling between voltage sensors and activation gate in voltage-gated K+ channels. J Gen Physiol 120, 663-676. Lu Z & MacKinnon R. (1994). Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel. Nature 371, 243-246. MacKinnon R. (1991). Determination of the subunit stoichiometry of a voltage-activated potassium channel. Nature 350, 232-235. MacKinnon R, Heginbotham L & Abramson T. (1990). Mapping the receptor site for charybdotoxin, a pore-blocking potassium channel inhibitor. Neuron 5, 767-771. MacKinnon R & Miller C. (1989). Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science 245, 1382-1385. Matsuda H. (1988). Open-state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea-pig heart cells. J Physiol 397, 237-258. Matsuda H. (1991). Effects of external and internal K+ ions on magnesium block of inwardly rectifying K+ channels in guinea-pig heart cells. J Physiol 435, 83-99. Matsuda H, Hayashi M & Okada M. (2010). Voltage-dependent block by internal spermine of the murine inwardly rectifying K+ channel, Kir 2.1, with asymmetrical K+ concentrations. J Physiol 588, 4673-4681. Matsuda H, Oishi K & Omori K. (2003). Voltage-dependent gating and block by internal spermine of the murine inwardly rectifying K+ channel, Kir 2.1. J Physiol 548, 361-371. McKinney LC & Gallin EK. (1988). Inwardly rectifying whole-cell and single-channel K currents in the murine macrophage cell line J774.1. J Membr Biol 103, 41-53. Miyashita T & Kubo Y. (1997). Localization and developmental changes of the expression of two inward rectifying K(+)-channel proteins in the rat brain. Brain Res 750, 251-263. Mott NF, Gurney, R.W. (1940). Electronic Process in Ionic Crystals. Oxford University, Oxford. Nagao Y, Harada Y, Mukai T, Shimizu S, Okuda A, Fujimoto M, Ono A, Sakagami Y & Ohno Y. (2013). Expressional analysis of the astrocytic Kir4.1 channel in a pilocarpine-induced temporal lobe epilepsy model. Frontiers in cellular neuroscience 7, 104. Neusch C, Weishaupt JH & Bahr M. (2003). Kir channels in the CNS: emerging new roles and implications for neurological diseases. Cell Tissue Res 311, 131-138. Nichols CG & Lopatin AN. (1997). Inward rectifier potassium channels. Annu Rev Physiol 59, 171-191. Nishida M, Cadene M, Chait BT & MacKinnon R. (2007). Crystal structure of a Kir3.1-prokaryotic Kir channel chimera. EMBO J 26, 4005-4015. Oishi K, Omori K, Ohyama H, Shingu K & Matsuda H. (1998). Neutralization of aspartate residues in the murine inwardly rectifying K+ channel IRK1 affects the substate behaviour in Mg2+ block. J Physiol 510 ( Pt 3), 675-683. Okada M & Matsuda H. (2008). Chronic lentiviral expression of inwardly rectifying K+ channels (Kir 2.1) reduces neuronal activity and downregulates voltage-gated potassium currents in hippocampus. Neuroscience 156, 289-297. Oliver D, Baukrowitz T & Fakler B. (2000). Polyamines as gating molecules of inward-rectifier K+ channels. Eur J Biochem 267, 5824-5829. Oliver D, Hahn H, Antz C, Ruppersberg JP & Fakler B. (1998). Interaction of permeant and blocking ions in cloned inward-rectifier K+ channels. Biophys J 74, 2318-2326. Osawa M, Yokogawa M, Muramatsu T, Kimura T, Mase Y & Shimada I. (2009). Evidence for the direct interaction of spermine with the inwardly rectifying potassium channel. J Biol Chem 284, 26117-26126. Pegan S, Arrabit C, Zhou W, Kwiatkowski W, Collins A, Slesinger PA & Choe S. (2005). Cytoplasmic domain structures of Kir 2.1 and Kir3.1 show sites for modulating gating and rectification. Nat Neurosci 8, 279-287. Preisig-Muller R, Schlichthorl G, Goerge T, Heinen S, Bruggemann A, Rajan S, Derst C, Veh RW & Daut J. (2002). Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome. Proc Natl Acad Sci U S A 99, 7774-7779. Pruss H, Derst C, Lommel R & Veh RW. (2005). Differential distribution of individual subunits of strongly inwardly rectifying potassium channels (Kir2 family) in rat brain. Brain Res Mol Brain Res 139, 63-79. Reimann F & Ashcroft FM. (1999). Inwardly rectifying potassium channels. Curr Opin Cell Biol 11, 503-508. Reimann F, Ryder TJ, Tucker SJ & Ashcroft FM. (1999a). The role of lysine 185 in the kir6.2 subunit of the ATP-sensitive channel in channel inhibition by ATP. J Physiol 520 Pt 3, 661-669. Reimann F, Tucker SJ, Proks P & Ashcroft FM. (1999b). Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor. J Physiol 518 ( Pt 2), 325-336. Robertson JL, Palmer LG & Roux B. (2012). Multi-ion distributions in the cytoplasmic domain of inward rectifier potassium channels. Biophys J 103, 434-443. Sakmann B, Noma A & Trautwein W. (1983). Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature 303, 250-253. Salke-Kellermann RA, May T & Boenigk HE. (1997). Influence of ethosuximide on valproic acid serum concentrations. Epilepsy Res 26, 345-349. Sarkisova KY, Kuznetsova GD, Kulikov MA & van Luijtelaar G. (2010). Spike-wave discharges are necessary for the expression of behavioral depression-like symptoms. Epilepsia 51, 146-160. Sayer RJ, Brown AM, Schwindt PC & Crill WE. (1993). Calcium currents in acutely isolated human neocortical neurons. J Neurophysiol 69, 1596-1606. Schram G, Melnyk P, Pourrier M, Wang Z & Nattel S. (2002). Kir2.4 and Kir 2.1 K(+) channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity. J Physiol 544, 337-349. Schrempf H, Schmidt O, Kummerlen R, Hinnah S, Muller D, Betzler M, Steinkamp T & Wagner R. (1995). A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans. EMBO J 14, 5170-5178. Shaw FZ, Chuang SH, Shieh KR & Wang YJ. (2009). Depression- and anxiety-like behaviors of a rat model with absence epileptic discharges. Neuroscience 160, 382-393. Shiau YS, Huang PT, Liou HH, Liaw YC, Shiau YY & Lou KL. (2003). Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels. Chem Res Toxicol 16, 1217-1225. Shieh RC, Chang JC & Arreola J. (1998). Interaction of Ba2+ with the pores of the cloned inward rectifier K+ channels Kir 2.1 expressed in Xenopus oocytes. Biophys J 75, 2313-2322. Shieh RC, John SA, Lee JK & Weiss JN. (1996). Inward rectification of the IRK1 channel expressed in Xenopus oocytes: effects of intracellular pH reveal an intrinsic gating mechanism. J Physiol 494 ( Pt 2), 363-376. Shin HG & Lu Z. (2005). Mechanism of the voltage sensitivity of IRK1 inward-rectifier K+ channel block by the polyamine spermine. J Gen Physiol 125, 413-426. Shin HG, Xu Y & Lu Z. (2005). Evidence for sequential ion-binding loci along the inner pore of the IRK1 inward-rectifier K+ channel. J Gen Physiol 126, 123-135. Signorini S, Liao YJ, Duncan SA, Jan LY & Stoffel M. (1997). Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2. Proc Natl Acad Sci U S A 94, 923-927. Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA & Lifton RP. (1996a). Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet 13, 183-188. Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA & Lifton RP. (1996b). Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet 14, 152-156. Slaght SJ, Leresche N, Deniau JM, Crunelli V & Charpier S. (2002). Activity of thalamic reticular neurons during spontaneous genetically determined spike and wave discharges. J Neurosci 22, 2323-2334. Spassova M & Lu Z. (1998). Coupled ion movement underlies rectification in an inward-rectifier K+ channel. J Gen Physiol 112, 211-221. Stampe P & Begenisich T. (1998). Unidirectional fluxes through ion channels expressed in Xenopus oocytes. Methods Enzymol 293, 556-564. Stanfield PR, Davies NW, Shelton PA, Sutcliffe MJ, Khan IA, Brammar WJ & Conley EC. (1994). A single aspartate residue is involved in both intrinsic gating and blockage by Mg2+ of the inward rectifier, IRK1. J Physiol 478 ( Pt 1), 1-6. Steinhauser C & Seifert G. (2002). Glial membrane channels and receptors in epilepsy: impact for generation and spread of seizure activity. Eur J Pharmacol 447, 227-237. Sunami A, Tracey A, Glaaser IW, Lipkind GM, Hanck DA & Fozzard HA. (2004). Accessibility of mid-segment domain IV S6 residues of the voltage-gated Na+ channel to methanethiosulfonate reagents. J Physiol 561, 403-413. Taglialatela M, Ficker E, Wible BA & Brown AM. (1995). C-terminus determinants for Mg2+ and polyamine block of the inward rectifier K+ channel IRK1. EMBO J 14, 5532-5541. Tao X, Avalos JL, Chen J & MacKinnon R. (2009). Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution. Science 326, 1668-1674. Thompson SM & Wong RK. (1991). Development of calcium current subtypes in isolated rat hippocampal pyramidal cells. J Physiol 439, 671-689. Ussing HH. (1949). Transport of ions across cellular membranes. Physiol Rev 29, 127-155. Vandenberg CA. (1987). Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc Natl Acad Sci U S A 84, 2560-2564. Vrielynck P. (2013). Current and emerging treatments for absence seizures in young patients. Neuropsychiatr Dis Treat 9, 963-975. Watanabe S, Kusama-Eguchi K, Kobayashi H & Igarashi K. (1991). Estimation of polyamine binding to macromolecules and ATP in bovine lymphocytes and rat liver. J Biol Chem 266, 20803-20809. Wickman K, Nemec J, Gendler SJ & Clapham DE. (1998). Abnormal heart rate regulation in GIRK4 knockout mice. Neuron 20, 103-114. Woodhull AM. (1973). Ionic blockage of sodium channels in nerve. J Gen Physiol 61, 687-708. Xie LH, John SA & Weiss JN. (2002). Spermine block of the strong inward rectifier potassium channel Kir 2.1: dual roles of surface charge screening and pore block. J Gen Physiol 120, 53-66. Xie LH, John SA & Weiss JN. (2003). Inward rectification by polyamines in mouse Kir 2.1 channels: synergy between blocking components. J Physiol 550, 67-82. Xu Y, Shin HG, Szep S & Lu Z. (2009). Physical determinants of strong voltage sensitivity of K(+) channel block. Nat Struct Mol Biol 16, 1252-1258. Yamada A, Uesaka N, Hayano Y, Tabata T, Kano M & Yamamoto N. (2010). Role of pre- and postsynaptic activity in thalamocortical axon branching. Proc Natl Acad Sci U S A 107, 7562-7567. Yang J, Jan YN & Jan LY. (1995a). Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel. Neuron 14, 1047-1054. Yang J, Jan YN & Jan LY. (1995b). Determination of the subunit stoichiometry of an inwardly rectifying potassium channel. Neuron 15, 1441-1447. Yang YC, Lee CH & Kuo CC. (2010). Ionic flow enhances low-affinity binding: a revised mechanistic view into Mg2+ block of NMDA receptors. J Physiol 588, 633-650. Yeh SH, Chang HK & Shieh RC. (2005). Electrostatics in the cytoplasmic pore produce intrinsic inward rectification in Kir 2.1 channels. J Gen Physiol 126, 551-562. Yellen G, Jurman ME, Abramson T & MacKinnon R. (1991). Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel. Science 251, 939-942. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58810 | - |
dc.description.abstract | 內向整流性鉀離子通道(Kir通道)最主要特徵就是在生理情況下,會使往細胞膜內通過的鉀離子電導遠大於往細胞膜外通過的鉀離子電導,因此呈現向內整流的特性。從生理學的角度而言,這類型的內向整流性鉀離子通道所具有的離子電導特性,主要是既能維持細胞膜的靜止膜電位,將細胞膜的靜止膜電位接近於鉀離子的平衡電位。又能在進行去極化的過程中,避免細胞內過多的鉀離子排出細胞膜外。目前為止,認為此種內向整流性的特性,起因於細胞膜內的內生性多聚合胺(例如:精胺)阻塞Kir通道,因而阻塞鉀離子的外向電流。不過細胞膜內的內生性精胺造成阻塞的效果,並不能完全以電壓依賴特性來解釋,精胺阻塞Kir通道造成內向整流特性,很有可能起因於精胺本身和該離子通道內的可通透離子之間存在著流向偶合的特性。
本論文利用分子生物學突變技術、電生理記錄方式與分子動態模擬方式,探討與瞭解精胺在內向整流性Kir 2.1通道的結合位置、精胺和Kir 2.1通道內可通透性離子的作用、及Kir 2.1通道本身門閥開關機制三者之間的作用關係。研究結果發現精胺阻塞Kir 2.1的親和力曲線明顯會隨著鉀離子平衡電位的移動。精胺結合於Kir 2.1通道的動力學分析,發現當突變Kir 2.1通道的細胞膜內區域中E224和E299氨基酸後,明顯減小精胺的進入孔洞的結合速率,這現象反應出突變此兩個胺基酸後,會破壞精胺和可通透離子之間的流向依賴及流向偶合的性質。實驗指出無論是野生型Kir 2.1通道抑或是突變兩個胺基酸(E224及E299)後,精胺的結合速率和脫離速率具有少許的電壓依賴特性。藉由精胺在Kir 2.1通道內的動力學分析以及電壓依賴特性。我們發現精胺阻塞Kir 2.1的結合位置位於從該通道的細胞質區域算起約0.5電距離,並且精胺與通道內可通透的鉀離子流向偶合位置在於四個次單位蛋白螺旋交會區域。當鉀離子往細胞膜外流出後,精胺受鉀離子外向電流推往Kir 2.1通道中四個次單位蛋白螺旋交會區域最外端的位置(即D172)。另一方面,隨著鉀離子流向的改變(例如:向內電流),則可以將精胺推往該區域較內端的位置(大約在M183到A184)。實驗也發現雙突變E224及A178(或是M183)胺基酸後,將會改變精胺在Kir 2.1通道中細胞質內結構和結合位置之間不對稱障礙的高度。而且在Kir 2.1通道的細胞質內區域結構中E224和E299極有可能和其他正電的胺基酸(例如:R228和R260),透過異位性作用方式開啟該通道的四個次單位蛋白螺旋交會區域,讓精胺可以透過和鉀離子流向偶合作用阻塞該通道,進而造成內向整流特性。 Kir 2.1通道的四個次單位蛋白螺旋交會區域同時也是該通道門閥開關機制中極為重要區域。我們發現突變氨基酸A184R後,不僅會改變原有精胺阻塞該通道所造成的內向整流特性,更可以使得該通道孔洞趨向於關閉狀態,並且也發現細胞內的陽離子可以作用在該通道的細胞質內結構使A184R突變通道孔洞趨向開啟狀態。我們也進一步發現Kir 2.1通道孔洞可以同時結合兩個以上的精胺。會嚴重阻塞Kir 2.1通道的是位於較深位置的精胺,其位置與阻塞效果是具有流向依賴性特性。結合在該通道內淺層區域(較近通道內口區域)的精胺,則可以打開該通道孔洞之門閥,加速深層位置精胺的脫離速率。因此精胺在內向整流性鉀離子通道不僅是扮演孔洞的阻塞物質,同時也扮演Kir 2.1的孔洞內門閥開關的物質。 除此以外,我們也進一步進行藥物阻塞Kir 2.1通道的分子藥理機轉。Ethusuximide (ETX)藥物在臨床上經常選擇性使用於治療癲癇小發作(petil mal)的病患。在癲癇動物模式的研究發現,Kir通道對於癲癇的致病機轉有其關聯性。我們利用分子生物學突變技術、電生理記錄方式與分子動態模擬方式,進行ETX結合於Kir 2.1通道的親和力以及動力學分析。實驗結果證明ETX會抑制Kir 2.1通道的外向鉀離子電流,且具有明顯的濃度依賴特性;而另一種Valproic acid (VPA)藥物則不具有此抑制作用。我們的結果更可以進一步推論出ETX是透過與鉀離子偶合作用(在細胞內外有對稱性100 mM K+的溶液情況下,ETX應是與1.2個鉀離子相互偶合),在主要是外向電流的情況下,被推往Kir 2.1通道中四個次單位蛋白螺旋交會區域最外端的位置(即S165–T141附近)。另一方面,隨著鉀離子流向改變為主要係內向電流時,則可以將ETX推往該通道中四個次單位蛋白螺旋交會區域最內端的位置。綜合實驗結果以上,我們結論Kir 2.1通道中四個次單位蛋白螺旋交會區域,對於通道之運作而言,兼具有重要的生理與藥理意義。不僅與內生性的精胺及抗癲癇藥物ETX阻塞Kir 2.1通道造成內向整流的特性密切相關,同時也是造成離子通透與通道門閥開關相互作用的關鍵區域。 | zh_TW |
dc.description.abstract | Inward rectifier K+ channels (Kir channels) conduct K+ ions across the cell membrane inwardly much larger than outwardly in physiological conditions. This intriguing conduction property is essential for the physiological function of these channels, including the maintenance of the resting membrane potential close to the K+ equilibrium potential without excessively losing the intracellular K+ to the extracellular compartment during membrane depolarization. The mechanism underlying the intriguing inward rectification phenomenon in the Kir channel has been ascribed mostly to intracellular polyamines (e.g., spermine, SPM) block of the pore. Voltage–dependent and flow–dependent block of outward K+ currents by intracellular SPM has been proposed as the major mechanisms underlying inward rectification.
In this study, we show that the SPM blocking affinity curve is shifted according to the shift in K+ reversal potential. The inhibition of the outward currents by the SPM has been shown dependent on the driving force (Vm–EK+) which is equivalent to the different of the electrochemical potentials. Moreover, the kinetics of SPM entry to and exit from the binding site are correlatively slowed by specific E224 and E299 mutations, which always also disrupt the flux–coupling feature of SPM block. The entry rates carry little voltage dependence, whereas the exit rates are e–fold decelerated per ~15 mV depolarization. Interestingly, the voltage dependence remains rather constant among WT and quite a few different mutant channels. This voltage dependence offers an unprecedented chance of mapping the location (electrical distance) of the SPM site in the pore, because these kinetic data were obtained along the preponderant direction of K+ current flow (outward currents for the entry rate and inward currents for the exit rate) and thus contamination from flow dependence should be negligible. Moreover, double mutations involving E224 and A178 or M183 seem to alter the height of the same asymmetrical barrier between the SPM binding site and the intracellular melieu. We conclude that the SPM site responsible for the inward rectifying block is located at electrical distance ~0.5 from the inside and is involved in a flux–coupling segment in the bundle crossing region of the pore. With preponderant outward K+ flow, SPM is “pushed” to the outmost site of this segment (~D172). On the other hand, the blocking SPM would be pushed to the inner end of this segment (~M183–A184). Moreover, E224 and E299 very likely electrostatically interact with the other residues (e.g., R228, R260) in the cytoplasmic domain, and then allosterically keep the bundle crossing region in an open conformation appropriate for the flux–coupling block of SPM. Moreover, the bundle crossing region of the Kir 2.1 channel may undergo opening/closing conformational changes mimicking channel gating. We further investigate these “gating” conformational changes at this critical segment and demonstrate that A184R mutation in the inner end of the bundle crossing region not only abolishes the inward rectifying features of SPM block but also tends to close the channel pore, which can then only be opened by intracellular but not extracellular cations. This ionic site responsible for the opening of the A184R mutant channel is located in the cytoplasmic domain, and is not selective for K+ because intracellular Na+ is as effective as K+ in this action. We also found that the WT channel pore could accommodate at least 2 SPM molecules simultaneously, and the unbinding of the blocking SPM in the deep site is facilitated rather than deterred by the presence of the other SPM in the superficial site. We conclude that the SPM in the deep site serves as a flow–dependent pore blocker. The SPM in the superficial site, on the other hand, serves both as a docking form ready for permeation to the deep site, and as a gating particle capable of opening the bundle crossing region. In addition, we also studied the action of the pharmacological agent blocking of the Kir 2.1 channel. Ethosuximide (ETX), 2–ethyl–2–methylsuccinimide, is used clinical generally common for its selective effect on absence seizures. Many evidences on the seizure animal model have yielded information that Kir channels are implicated in seizure generation. We further examined the kinetics of ETX binding to and unbinding from the Kir 2.1 channel, as well as the binding affinity of ETX to this channel. We have demonstrated that the outward currents of the Kir 2.1 channel are inhibited by intracellular ETX with accelerated decay in a dose–dependent fashion, but not by valproic acid (VPA). We also found that ETX, most likely coming from the intracellular side, is “carried” by the outward K+ flux (i.e., accompanied by 1.2 K+ in symmetrical 100 mM K+) via the flux–coupling bundle crossing region to reach its block site between S165 and T141, and thus makes a flow– and voltage–dependent block of the Kir 2.1 channel pore. All these data indicate that the bundle crossing region of the Kir 2.1 channel pore thus constitutes a pivotal segment, which, in collaboration with internal SPM, ETX, and K+ ions, closely couple channel gating to inward rectifying ion permeation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:32:18Z (GMT). No. of bitstreams: 1 ntu-102-D94441001-1.pdf: 2763288 bytes, checksum: e31e80262f81f2bd57877f81c58dc56a (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | ACKNOWLEDGEMENTS……………………………………………………………...I
ABSTRACT IN CHINESE (中文摘要)………………………………………………...II ABSTRACT……………………………………………………………….....................V Chapter1 Introduction……….………………………………………………………1 1.1 Overview of inward rectifying potassium channels……………………………….2 1.2 Molecular structure of the Kir channels…………………………………………...3 1.2.1 Topology and structure of the Kir channels…………………………………….3 1.2.2 Structure of the KcsA channel similar to that of the Kir channels……………..6 1.2.3 The structural bases and pore function of the Kir 2.1 channel..………………..7 1.2.3.1 The cytoplasmic domain.………………………………………………...7 1.2.3.2 The bundle crossing region of the pore……………………………….....8 1.3 The mechanism of inward rectification of the Kir 2.1 channel..…………………..9 1.3.1 The voltage dependence block by polyamine and magnesium ions…………...9 1.3.2 The SPM blocks the Kir 2.1 channel by flux–dependence block…………….10 1.3.2.1 The SPM blocks the Kir 2.1 channel that deviates from the Woodhull model…………………………………………………………………...10 1.3.2.2 The flux–coupling effect…………………………………………….....12 1.3.2.3 The long pores have flux–coupling effects……………………………...12 1.4 The pharmacological effect of the Kir 2.1 channel.….....………………………..13 1.5 The scope of this study…………………………………………………………...15 Chapter2 Materials and methods……………………………………..……………16 2.1. Molecular biology and preparation of Xenopus oocytes…………………………17 2.2. Electrophysiological recordings………………………………………………….17 2.3. MTSEA modification…………………………………………………………….19 2.4. Homology modeling of the Kir 2.1 channel……………………………………...19 2.5. Molecular dynamics simulation………………………………………………….19 2.6. Data analysis……………………………………………………………………..20 2.7. Figures……………………………………………………………………………22 Chapter3 The bundle crossing region is responsible for the inwardly rectifying internal spermine block of the Kir 2.1 channel………………………..26 3.1 Results……………………………………………………………………………..27 3.1.1 Effects of reversal potential shift and K+ ions on internal SPM block in WT Kir 2.1 channels……………………………………………………………...27 3.1.2 The dramatic change of binding and unbinding kinetics of SPM when the direction of K+ flow is altered………………………………………………..28 3.1.3 Dramatic decrease of IR index and emergence of a slow unbinding phase of internal SPM block in specific E224 mutant channels………………………28 3.1.4 Negligible voltage dependence in the binding kinetics but strong voltage dependence in the unbinding kinetics of internal SPM……………………...29 3.1.5 Pore narrowing induced by E224 mutations at the bundle crossing region of TM2………………………………………………………………………….30 3.1.6 Similar voltage dependence in SPM unbinding kinetics in different mutant channels……………………………………………………………………...31 3.1.7 The same pore–narrowing effect of E299 mutation as that of E224………...31 3.1.8 The slow tail of SPM unblock is present in pHi 6.4 but not 8.4 in the E299H mutant channel at –100 mV………………………………………………….32 3.1.9 Elimination of the slow tail in the E224 and E299 mutant channels by concomitant mutations of R228 and R260…………………………………..33 3.1.10 Profound decrease of IR index in the D172N but not S165L mutant channels……………………………………………………………………...33 3.2 Discussion………………………………………………………………………....35 3.2.1 The SPM binding site is located in a flux–coupling segment of the pore…...35 3.2.2 The flux–coupling segment is separated from the inside with an electrical distance ~0.5 and a very asymmetrical energy barrier for SPM permeation...35 3.2.3 The bundle–crossing region constitutes the flux–coupling segment critical for SPM block of the Kir 2.1 channel pore……………………………………...36 3.2.4 The pore caliber can be so minimized at the bundle crossing region as to markedly slow the movement of SPM………………………………………37 3.2.5 E224/E299 allosterically controls the conformation of the bundle crossing region via electrostatic interactions with R228/R260………………………..38 3.3 Figures…………………………………………………………………………….40 Chapter4 Gating of the Kir 2.1 channel pore at the bundle crossing region by intracellular spermine and other cations………………………………72 4.1 Results……………………………………………………………………………..73 4.1.1 There is a large discrepancy between the kinetics of internal SPM block measured with or without pre–existing SPM………………………………..73 4.1.2 The discrepancy between the two different measurements gets smaller with fewer charges and smaller size of the blocker……………………………….74 4.1.3 The discrepancy in SPM blocking kinetics is markedly decreased or even is negligible in specific mutant Kir 2.1 channels………………………………74 4.1.4 The blocking SPM in the deep site unbinds faster with higher intracellular SPM………………………………………………………………………….75 4.1.5 Residue A184 plays a critical role in both inward rectification and channel gating………………………………………………………………………...76 4.1.6 A184R, E224G, and E224Q mutations increase the height of the same permeation barrier in the pore……………………………………………….76 4.1.7 The inward currents in the A184R mutant channel develop slowly in low internal K+……………………………………………………………………78 4.1.8 The slow component of inward currents in the A184H mutant channel is much more evident in pHi 6.4 than 8.4………………………………………79 4.2 Discussion………………………………………………………………………....81 4.2.1 Colocalization of intrinsic as well as extrinsic rectification and gating functions of the Kir 2.1 channel pore at ~A184……………………………..81 4.2.2 Contribution of the cations internal to the bundle crossing region to the opening of Kir 2.1 channel pore……………………………………………..82 4.2.3 The significance of an alanine residue at the critical position 184…………..83 4.2.4 Implication on the evolution of functional design of Kir channels………….84 4.3 Figures…………………………………………………………………………….86 Chapter5 Flow– and voltage– dependent blocking effect of the antiepileptic drug ethosuximide on the inward rectifier K+ (Kir 2.1) channel…………..111 5.1 Results…………………………………………………………………………...112 5.1.1 Inhibition of WT Kir 2.1 currents by internal ETX in symmetrcial 100 mM K+…………………………………………………………………………...112 5.1.2 Inhibition of WT Kir 2.1 currents by internal ETX in 4 mM external and 100 mM internal K+……………………………………………………………..112 5.1.3 The emergence of a slow component of internal ETX unblock in WT Kir 2.1 channels…………………………………………………………………….113 5.1.4 Negligible voltage dependence in the binding kinetics but strong voltage dependence in the unbinding kinetics of internal ETX…………………….113 5.1.5 Decreased voltage– and flow–dependence of ETX block in the E224G and M183N mutant channels…………………………………………………...114 5.1.6 Profound decrease of the blocking effect of ETX in the S165L but not D172N mutant channels……………………………………………………………115 5.2 Discussion……………………………………………………………………….116 5.2.1 ETX blocks the Kir 2.1 channel pore at the external end of the central cavity with outward K+ currents……….…………………………………………..116 5.2.2 The movement of ETX in flux–coupling region of the Kir 2.1 channel pore is accompanied by ~1.2 K+ ions in 100 mM ambient K+……………………..117 5.2.3 The anti–absence effect of ETX may be contributed by mild neuronal depolarization ascribable to the Kir 2.1 channel block…………………….118 5.3 Figures…………………………………………………………………………...120 Chapter 6 Conclusions…………………………………………………………….141 Bibliography…………………………………………………………….……………144 | |
dc.language.iso | en | |
dc.title | Kir2.1離子通道的內向整流特性及藥理調節之分子機制 | zh_TW |
dc.title | Molecular Mechanisms Underlying the Inward Rectification and Pharmacological Modulation of the Kir2.1 Channel | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 陳順勝,蔡明正,謝如姬,湯志永,黃榮棋 | |
dc.subject.keyword | 內向整流性鉀離子通道,次單位蛋白螺旋交會區域,門閥開關,離子通透,流向耦合特性,電壓依賴特性, | zh_TW |
dc.subject.keyword | inwardly rectifying K+ channel,bundle crossing region,gating,permeation,flow–dependent block,voltage–dependent block, | en |
dc.relation.page | 155 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-12-17 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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