WATER AND H+ TRANSFER IN VOLTAGE GATED K+ CHANNEL FUNCTION, WITH EVIDENCE FROM QUANTUM CALCULATIONS.
Main Article Content
Abstract
Voltage gated K+ channels have been the subject of intensive study for over a half century. They are found in all cells; together with Na+ channels, they are responsible for the nerve impulse, and play a key role in other excitable tissue, particularly the heart. Malfunctions due to mutation lead to a range of diseases, referred to as channelopathies. The mechanism by which the channels open and close, called gating, has been studied extensively; there is a range of standard models. All have in common a transmembrane segment of the channel protein moving in response to depolarization of the membrane, thereby pulling open a section of the channel at the intracellular end of the membrane; this allows K+ ions into the channel pore, producing a current of ions out from the cell. The motion of the ions is preceded by a capacitative current, the gating current, which is attributed to positive charges on the putatively mobile transmembrane segment. The evidence supporting this class of models is examined and reinterpreted to show that the evidence does not require the motion of a segment of protein. This and other evidence is instead considered in terms of a model in which protons provide the gating current; when these are at the intracellular terminus of the protein, they close the channel, while the channel is open when they are at the extracellular end. This model is supported by quantum calculations that are larger than have been previously reported for a protein system. Some of the calculations include most of the voltage sensing domain, and others the pore of the channel, with the hydration and cosolvation of the ion specified.
Article Details
How to Cite
GREEN, Michael E; KARIEV, Alisher M.
WATER AND H+ TRANSFER IN VOLTAGE GATED K+ CHANNEL FUNCTION, WITH EVIDENCE FROM QUANTUM CALCULATIONS..
Medical Research Archives, [S.l.], v. 4, n. 7, nov. 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/725>. Date accessed: 04 dec. 2024.
Keywords
Ion channels, gating, solvation, voltage sensing domain, quantum calculations
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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Hodgkin, A. L. and A. F. Huxley (1952). "The dual effect of membrane potential on sodium conductance in the giant axon of Loligo." J. Physiol. (Lond) 116: 497-506.
Ishida, I. G., G. E. Rangel-Yescas, J. Carrasco-Zanini and L. D. Islas (2015). "Voltage-dependent gating and gating charge measurements in the Kv1.2 potassium channel." J. Gen. Physiol. 145(4): 345-358.
Jensen, M. O., V. Jogini, D. W. Borhani, A. E. Leffler, R. O. Dror and D. E. Shaw (2012). "Mechanism of voltage gating in potassium channels." Science (Washington, DC, U. S.) 336(Copyright (C) 2012 American Chemical Society (ACS). All Rights Reserved.): 229-233.
Kariev, A. M. and M. E. Green (2009). "Quantum calculations on water in the KcsA channel cavity with permeant and non-permeant ions." Biochim. Biophys. Acta (Biomembranes) 1788: 1188-1192.
Kariev, A. M. and M. E. Green (2012). "Voltage Gated Ion Channel Function: Gating, Conduction, and the Role of Water and Protons." Int'l J. Molec. Sci. 13: 1680-1709.
Kariev, A. M. and M. E. Green (2015). "Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms." Int. J. Mol. Sci. 16(1): 1627-1643.
Kariev, A. M. and M. E. Green (2015). "Quantum Effects in a Simple Ring with Hydrogen Bonds " J. Phys. Chem. B 119: 5962-5969.
Karlin, A. and M. H. Akabas (1998). "Substituted-cysteine accessibility method." Methods in Enzymology 293: 123-145.
Keynes, R. D. and E. Rojas (1974). "Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon." J. Physiol. (Lond.) 239: 393-434.
Kim, J.-B. (2014). " Channelopathies." Korean J. Pediatr 57: 1-18.
Kintzer, A. F. and R. M. Stroud (2016). "Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana." Nature (London, U. K.) 531(7593): 258-264.
Kosolapov, A., L. Tu, J. Wang and C. Deutsch (2004). "Structure acquisition of the T1 domain of Kv1.3 during biogenesis." Neuron 44(2): 295-307.
LeMasurier, M., L. Heginbotham and C. Miller (2001). "KcsA: It's a potassium channel." J. Gen'l Physiol. 118: 303-313.
Liao, S. and M. E. Green (2011). "Quantum calculations on salt bridges with water: Potentials, structure, and properties." Comput. Theo. Chem 963: 207-214.
Long, S. B., E. B. Campbell and R. MacKinnon (2005). "Crystal structure of a mammalian voltage-dependent Shaker family K+ channel " Science 309: 897-903.
Minor, D. L., Jr., Y.-F. Lin, B. C. Mobley, A. Avelar, Y. N. Jan, L. Y. Jan and J. M. Berger (2000). "The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel." Cell (Cambridge, Mass.) 102(5): 657-670.
Moroni, A. and G. Thiel (2006). "Flip-flopping salt bridges gate an ion-channel." Nat. Chem. Biol 2: 572-573.
Nguyen, T. P. and R. Horn (2002). "Movement and crevices around a sodium channel S3 segment." J. Gen'l. Physiol. 120: 419-436.
Noda, M., T. Shimizu, T. Tanabe, T. Takai, T. Kayano, T. Ikeda, H. Takahashi, H. Nakayama, N. Kanaoka, N. Minamino, K. Kangawa, H. Matsuo, M. A. Raftery, T. Hirose, S. Inayama, H. Hayashida, T. Miyata and S. Numa (1984). "Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence." Nature 312: 121-127.
Papazian, D. M., X. M. Shao, S.-A. Seoh, A. F. Mock, Y. Huang and D. H. Wainstock (1995). "Electrostatic interactions of S4 voltage sensor in Shaker K+ channel." Neuron 14: 1293-1301.
Pinental, D., J. M. Donlea, C. B. Talbot, S. M. Song, A. J. F. Thurston and G. Miiesenbock (2016). "Operation of a Homeostatic Sleep Switch." Nature.
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