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J. Biol. Chem., Vol. 277, Issue 12, 10523-10530, March 22, 2002
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From the Department of Physiology, University of Tennessee Health
Science Center, Memphis, Tennessee 38163
Intracellular application of certain
charged methanethiosulfonate (MTS) reagents modified and irreversibly
inhibited Kir6.2 channels when cysteine substitutions were introduced
at positions Ile-210, Ile-211, or Ser-212 within the putative
cytoplasmic region. Inhibition depends on the spatial dimensions of the
MTS reagents. Reaction of MTS reagents, having head diameters of
7.6-8.2 Å, with cysteines introduced at position Ser-212 must occur
in more than two subunits of the tetrameric Kir6.2 complex to inhibit channel activity. MTS reagents with head diameters less than 6.6 Å modified cysteines without causing channel inhibition. An MTS reagent
with a head diameter of ~10 Å could neither modify nor inhibit the
channels. Channel inhibition is interpreted as blockage of the
intracellular vestibule by MTS reagents that enter the channel
vestibule and react with the cysteine residues at vestibule-lining positions. Data are consistent with the hypothesis that residues Ile-210-Ser-212 line a funnel-shaped vestibule of 20-25 Å in
diameter, which remains unchanged during channel gating.
Cytoplasmic Vestibule of the Weak Inward Rectifier Kir6.2
Potassium Channel*
*
This work was supported by National Institutes of Health
Grants HL-58133 and GM61943 and by a grant-in-aid from the American Heart Association, Southeast Affiliate (to Z. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Physiology,
University of Tennessee Health Science Center, 894 Union Ave.,
Memphis, TN 38163. Tel.: 901-448-2872; Fax: 901-448-7126; E-mail: zfan@physio1.utmem.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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