HYdrogen peroxide activates k+ channels in llc-pk1 cells

Dragana M. Filipovic, W. Brian Reeves

Research output: Contribution to journalArticle

Abstract

Oxidant-induced damage has been implicated in the pathogenesis of several forms of cellular injury. The activation of K+ channels appears to be an early event in injury of renal tubular epithelial cells (Reeves and Shah, J. Clin. Invest. 94: 2289-2294, 1994). The present studies employed patch clamp methods to determine if oxidant stress leads to activation of plasma membrane K+ channels in the renal epithelial LLCPKi cell line. Cellular membrane potential was measured with the perforated whole cell current-clamp recording configuration. Exposure of these cells to H2U2 (0.1 mM to 5 mM) induced a rapid, dose-dependent membrane hyperpolarization. Whole cell voltage-clamp studies were performed to determine the ion selectivity of the currents underlying this H2U2-induced cellular hyperpolarization. H2U2 (5 mM) increased the whole cell current response to a 60 mV depolarizing pulse from 12.3 ± 1.6 pA/pF to 68.3 ±6.6 pA/pF (n = 5). In solutions where EK = -82 mV and ECI = 0 mV, the reversal potential of the H2U2-induced current was approximately -75 mV, consistent with a K+ selective conductance. This current was inhibited largely (84 ±9%) by barium (5 mM) and glibenclamide (500 |iM), but only partially by tetraethylamonium (15 mM). Single-channel studies revealed two types of Ca-independent, Kselective channels in the H202-treated cells: a 40-pS short-open time (5.3 ± 1.2 ms) channel (n =7). and a 20-pS long-open time (60 ±8 ms) channel (n =5). These findings indicate that H22 activates a Caindependent K+ conductance in LLC-PKi cells. This activation may have a role in the pathogenesis of oxidant-induced cell injury. Supported by the American Heart Association.

Original languageEnglish (US)
Pages (from-to)A73
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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