title: Fluid flow facilitates inward rectifier K+current by convectively restoring [K+] at the cell membrane surface.
abstract: The inward rectifier Kir2.1 current (IKir2.1) was reported to be facilitated by fluid flow. However, the mechanism underlying this facilitation remains uncertain. We hypothesized that during K+influx or efflux, [K+] adjacent to the outer mouth of the Kir2.1 channel might decrease or increase, respectively, compared with the average [K+] of the bulk extracellular solution, and that fluid flow could restore the original [K+] and result in the apparent facilitation of IKir2.1. We recorded the IKir2.1 in RBL-2H3 cells and HEK293T cells that were ectopically over-expressed with Kir2.1 channels by using the whole-cell patch-clamp technique. Fluid-flow application immediately increased the IKir2.1, which was not prevented by either the pretreatment with inhibitors of various protein kinases or the modulation of the cytoskeleton and caveolae. The magnitudes of the increases of IKir2.1 by fluid flow were driving force-dependent. Simulations performed using the Nernst-Planck mass equation indicated that [K+] near the membrane surface fell markedly below the average [K+] of the bulk extracellular solution during K+influx, and, notably, that fluid flow restored the decreased [K+] at the cell surface in a flow rate-dependent manner. These results support the "convection-regulation hypothesis" and define a novel interpretation of fluid flow-induced modulation of ion channels.
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, South Korea.
authors.forename: Jae Gon
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Emergency Medical Services, Eulji University, Seongnam, Gyeonggi-do, 461-713, South Korea.
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, Sungkyunkwan University, 2066 Seobu-Ro, Jangan-Gu, Suwon, Gyeonggi, 440-746, South Korea.
authors.forename: Doyoung
authors.initials: D
authors.lastname: Byun
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Division of Sport Science, College of Science and Technology, Konkuk University, Chungju, 380-701, South Korea.
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Sung
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, South Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Shin
authors.affiliation: Department of Physiology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Leem
authors.affiliation: Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Physiology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, South Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, South Korea.
authors.forename: Sung I
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Physiology, KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, South Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D015638:Cytochalasin D / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D004594:Electrophysiology; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007477:Ions; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010590:Phalloidine / Q000737:chemistry; D011188:Potassium / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D051381:Rats; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000199:Actins; D007477:Ions; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D010590:Phalloidine; D015638:Cytochalasin D; D011188:Potassium