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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Kim JG,Park SW,Byun D,Choi WS,Sung DJ,Shin KC,Kim HJ,Leem YE,Kang JS,Cho H,Kim B,Cho SI,Bae YM

doi

10.1038/srep39585

subject

Has Abstract

pub_date

2016-12-22 00:00:00

pages

39585

issn

2045-2322

pii

srep39585

journal_volume

6

pub_type

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