title: The mechanism of inward rectification in Kir channels: A novel kinetic model with non-equilibrium thermodynamics approach.
abstract: The mechanisms of the strong inward rectification in inward rectifier K(+) (Kir) channels are controversial because the drop in electrical potential due to the movement of the blocker and coupling ions is insufficient to explain the steep voltage-dependent block near the equilibrium potential. Here, we study the "driving force"-dependent block in Kir channels with a novel approach incorporating concepts from the non-equilibrium thermodynamics of small systems, and computer kinetic simulations based on the experimental data of internal Ba(2+) block on Kir2.1 channels. The steep exponential increase in the apparent binding rate near the equilibrium potential is explained, when the encounter frequency is construed as the likelihood of transfer events down or against the electrochemical potential gradient. The exponent of flux ratio, nf=2.62, implies that the blockage of the internal blocker may be coupled with the outward transport of 2 to 3K(+) ions. The flux-coupled block in the single-file multi-ion pore can be demonstrated by the concentration gradient alone, as well as when the driving force is the electrochemical potential difference across the membrane.
authors.affiliation: Department of Medical Education, Far Eastern Memorial Hospital, No. 21, Nan-Ya S. Rd., Ban-Chiao, New Taipei City 220, Taiwan; Department of Family Medicine, Far Eastern Memorial Hospital, No. 21, Nan-Ya S. Rd., Ban-Chiao, New Taipei City 220, Taiwan; Center for General Education, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung-Li District, Taoyuan City 320, Taiwan. Electronic address: hsiehcp@ntu.edu.tw.
authors.forename: Chi-Pan
authors.initials: CP
authors.lastname: Hsieh
authors.affiliation: Department of Medical Education, Far Eastern Memorial Hospital, No. 21, Nan-Ya S. Rd., Ban-Chiao, New Taipei City 220, Taiwan.
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Chiang
authors.affiliation: Department of Physiology, National Taiwan University College of Medicine, No.1, Jen-Ai Road, 1st Section, Taipei 100, Taiwan.
authors.forename: Chiung-Wei
authors.initials: CW
authors.lastname: Huang
mesh_terms: D001464:Barium / Q000737:chemistry; D002413:Cations, Divalent; D002414:Cations, Monovalent; D003198:Computer Simulation; D007700:Kinetics; D011188:Potassium / Q000737:chemistry; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D002413:Cations, Divalent; D002414:Cations, Monovalent; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; D011188:Potassium
keywords: Driving force; Fluctuation theorem; Flux coupling; Inward rectification; Inward rectifier K(+) channel; Ussing flux ratio