HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Romey, G. Articles by Lazdunski, M. Search for Related Content PubMed PubMed Citation Articles by Romey, G. Articles by Lazdunski, M. Social Bookmarking                      What's this?

Volume 272, Number 27, Issue of July 4, 1997 pp. 16713-16716
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Molecular Mechanism and Functional Significance of the MinK Control of the KvLQT1 Channel Activity

(Received for publication, April 8, 1997, and in revised form, May 12, 1997)

Georges Romey , Bernard Attali ^§ , Christophe Chouabe , Ilane Abitbol ^§ , Eric Guillemare , Jacques Barhanin and Michel Lazdunski

From the  Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France and the ^§ Weizmann Institute of Science, Department of Neurobiology, 76100 Rehovot, Israel

The very slowly activating delayed rectifier K⁺ channel I_Ks is essential for controlling the repolarization phase of cardiac action potentials and K⁺ homeostasis in the inner ear. The I_Ks channel is formed via the assembly of two transmembrane proteins, KvLQT1 and MinK. Mutations in KvLQT1 are associated with a long QT syndrome that causes syncope and sudden death and also with deafness. Here, we show a new mode of association between ion channel forming subunits in that the cytoplasmic C-terminal end of MinK interacts directly with the pore region of KvLQT1. This interaction reduces KvLQT1 channel conductance from 7.6 to 0.58 picosiemens. However, because MinK also reveals a large number of previously silent KvLQT1 channels (× 60), the overall effect is a large increase (× 4) in the macroscopic K⁺ current. Conformational changes associated with the KvLQT1/MinK association create very slow and complex activation kinetics without much alteration in the deactivation process. Changes induced by MinK have an essential regulatory role in the development of this K⁺ channel activity upon repetitive electrical stimulation with a particular interest in tachycardia.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Z. Gao, Q. Xiong, H. Sun, and M. Li Desensitization of Chemical Activation by Auxiliary Subunits: CONVERGENCE OF MOLECULAR DETERMINANTS CRITICAL FOR AUGMENTING KCNQ1 POTASSIUM CHANNELS J. Biol. Chem., August 15, 2008; 283(33): 22649 - 22658. [Abstract] [Full Text] [PDF]

				D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]

				W.-K. Lee, B. Torchalski, E. Roussa, and F. Thevenod Evidence for KCNQ1 K+ channel expression in rat zymogen granule membranes and involvement in cholecystokinin-induced pancreatic acinar secretion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C879 - C892. [Abstract] [Full Text] [PDF]

				H. S. Jensen, M. Grunnet, and S.-P. Olesen Inactivation as a New Regulatory Mechanism for Neuronal Kv7 Channels Biophys. J., April 15, 2007; 92(8): 2747 - 2756. [Abstract] [Full Text] [PDF]

				I. H. Quraishi and R. M. Raphael Computational model of vectorial potassium transport by cochlear marginal cells and vestibular dark cells Am J Physiol Cell Physiol, January 1, 2007; 292(1): C591 - C602. [Abstract] [Full Text] [PDF]

				K. D. Chandrasekhar, T. Bas, and W. R. Kobertz KCNE1 Subunits Require Co-assembly with K+ Channels for Efficient Trafficking and Cell Surface Expression J. Biol. Chem., December 29, 2006; 281(52): 40015 - 40023. [Abstract] [Full Text] [PDF]

				T. Jespersen, M. Grunnet, and S.-P. Olesen The KCNQ1 Potassium Channel: From Gene to Physiological Function Physiology, December 1, 2005; 20(6): 408 - 416. [Abstract] [Full Text] [PDF]

				D. Thomas, A.-B. Wimmer, C. A. Karle, M. Licka, M. Alter, M. Khalil, H. E. Ulmer, S. Kathofer, J. Kiehn, H. A. Katus, et al. Dominant-negative IKs suppression by KCNQ1-{Delta}F339 potassium channels linked to Romano-Ward syndrome Cardiovasc Res, August 15, 2005; 67(3): 487 - 497. [Abstract] [Full Text] [PDF]

				S. Bendahhou, C. Marionneau, K. Haurogne, M.-M. Larroque, R. Derand, V. Szuts, D. Escande, S. Demolombe, and J. Barhanin In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart Cardiovasc Res, August 15, 2005; 67(3): 529 - 538. [Abstract] [Full Text] [PDF]

				G. Seebohm, P. Westenskow, F. Lang, and M. C Sanguinetti Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels J. Physiol., March 1, 2005; 563(2): 359 - 368. [Abstract] [Full Text] [PDF]

				J. Qu, Y. Kryukova, I. A. Potapova, S. V. Doronin, M. Larsen, G. Krishnamurthy, I. S. Cohen, and R. B. Robinson MiRP1 Modulates HCN2 Channel Expression and Gating in Cardiac Myocytes J. Biol. Chem., October 15, 2004; 279(42): 43497 - 43502. [Abstract] [Full Text] [PDF]

				M. Grunnet, H. B. Rasmussen, A. Hay-Schmidt, M. Rosenstierne, D. A. Klaerke, S.-P. Olesen, and T. Jespersen KCNE4 Is an Inhibitory Subunit to Kv1.1 and Kv1.3 Potassium Channels Biophys. J., September 1, 2003; 85(3): 1525 - 1537. [Abstract] [Full Text] [PDF]

				L. Ma, C. Lin, S. Teng, Y. Chai, R. Bahring, V. Vardanyan, L. Li, O. Pongs, and R. Hui Characterization of a novel Long QT syndrome mutation G52R-KCNE1 in a Chinese family Cardiovasc Res, September 1, 2003; 59(3): 612 - 619. [Abstract] [Full Text] [PDF]

				H. Chen, F. Sesti, and S. A. N. Goldstein Pore- and State-Dependent Cadmium Block of IKs Channels Formed with MinK-55C and Wild-Type KCNQ1 Subunits Biophys. J., June 1, 2003; 84(6): 3679 - 3689. [Abstract] [Full Text] [PDF]

				E. Yus-Najera, I. Santana-Castro, and A. Villarroel The Identification and Characterization of a Noncontinuous Calmodulin-binding Site in Noninactivating Voltage-dependent KCNQ Potassium Channels J. Biol. Chem., August 2, 2002; 277(32): 28545 - 28553. [Abstract] [Full Text] [PDF]

				Y. F. Melman, A. Krumerman, and T. V. McDonald A Single Transmembrane Site in the KCNE-encoded Proteins Controls the Specificity of KvLQT1 Channel Gating J. Biol. Chem., July 5, 2002; 277(28): 25187 - 25194. [Abstract] [Full Text] [PDF]

				K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]

				U. C. Hoppe, E. Marban, and D. C. Johns Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1 PNAS, April 24, 2001; 98(9): 5335 - 5340. [Abstract] [Full Text] [PDF]

				L. Virag, N. Iost, M. Opincariu, J. Szolnoky, J. Szecsi, G. Bogats, P. Szenohradszky, A. Varro, and J. Gy. Papp The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes Cardiovasc Res, March 1, 2001; 49(4): 790 - 797. [Abstract] [Full Text] [PDF]

				M. H. Saier Jr. A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters Microbiol. Mol. Biol. Rev., June 1, 2000; 64(2): 354 - 411. [Abstract] [Full Text] [PDF]

				A. Murray, C. Donger, C. Fenske, I. Spillman, P. Richard, Y. B. Dong, N. Neyroud, P. Chevalier, I. Denjoy, N. Carter, et al. Splicing Mutations in KCNQ1 : A Mutation Hot Spot at Codon 344 That Produces In Frame Transcripts Circulation, September 7, 1999; 100(10): 1077 - 1084. [Abstract] [Full Text] [PDF]

				P. C Viswanathan and Y. Rudy Pause induced early afterdepolarizations in the long QT syndrome: a simulation study Cardiovasc Res, May 1, 1999; 42(2): 530 - 542. [Abstract] [Full Text] [PDF]

				N. Neyroud, P. Richard, N. Vignier, C. Donger, I. Denjoy, L. Demay, M. Shkolnikova, R. Pesce, P. Chevalier, B. Hainque, et al. Genomic Organization of the KCNQ1 K+ Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome Circ. Res., February 19, 1999; 84(3): 290 - 297. [Abstract] [Full Text] [PDF]

				W. Wang, J. Xia, and R. S. Kass MinK-KvLQT1 Fusion Proteins, Evidence for Multiple Stoichiometries of the Assembled IsK Channel J. Biol. Chem., December 18, 1998; 273(51): 34069 - 34074. [Abstract] [Full Text] [PDF]

				W.-P. Yang, P. C. Levesque, W. A. Little, M. L. Conder, P. Ramakrishnan, M. G. Neubauer, and M. A. Blanar Functional Expression of Two KvLQT1-related Potassium Channels Responsible for an Inherited Idiopathic Epilepsy J. Biol. Chem., July 31, 1998; 273(31): 19419 - 19423. [Abstract] [Full Text] [PDF]

				M.-D. Drici, I. Arrighi, C. Chouabe, J. R. Mann, M. Lazdunski, G. Romey, and J. Barhanin Involvement of IsK-Associated K+ Channel in Heart Rate Control of Repolarization in a Murine Engineered Model of Jervell and Lange-Nielsen Syndrome Circ. Res., July 13, 1998; 83(1): 95 - 102. [Abstract] [Full Text] [PDF]

				S. Demolombe, I. Baro, Y. Pereon, J. Bliek, R. Mohammad-Panah, H. Pollard, S. Morid, M. Mannens, A. Wilde, J. Barhanin, et al. A Dominant Negative Isoform of the Long QT Syndrome 1 Gene Product J. Biol. Chem., March 20, 1998; 273(12): 6837 - 6843. [Abstract] [Full Text] [PDF]

				G. Loussouarn, F. Charpentier, R. Mohammad-Panah, K. Kunzelmann, I. Baró, and D. Escande KvLQT1 Potassium Channel but Not IsK Is the Molecular Target for trans-6-Cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane Mol. Pharmacol., December 1, 1997; 52(6): 1131 - 1136. [Abstract] [Full Text]

				S. Kathofer, W. Zhang, C. Karle, D. Thomas, W. Schoels, and J. Kiehn Functional Coupling of Human beta 3-Adrenoreceptors to the KvLQT1/MinK Potassium Channel J. Biol. Chem., August 25, 2000; 275(35): 26743 - 26747. [Abstract] [Full Text] [PDF]

				G. Seebohm, C. R. Scherer, A. E. Busch, and C. Lerche Identification of Specific Pore Residues Mediating KCNQ1 Inactivation. A NOVEL MECHANISM FOR LONG QT SYNDROME J. Biol. Chem., April 20, 2001; 276(17): 13600 - 13605. [Abstract] [Full Text] [PDF]

				Y. F. Melman, A. Domenech, S. de la Luna, and T. V. McDonald Structural Determinants of KvLQT1 Control by the KCNE Family of Proteins J. Biol. Chem., February 23, 2001; 276(9): 6439 - 6444. [Abstract] [Full Text] [PDF]

				A. R. Tapper and A. L. George Jr. Location and Orientation of minK within the IKs Potassium Channel Complex J. Biol. Chem., October 5, 2001; 276(41): 38249 - 38254. [Abstract] [Full Text] [PDF]

				M. Zhang, M. Jiang, and G.-N. Tseng MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function : Potential Role as {beta} Subunit of Cardiac Transient Outward Channel? Circ. Res., May 25, 2001; 88(10): 1012 - 1019. [Abstract] [Full Text] [PDF]