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J. Biol. Chem., Vol. 277, Issue 24, 21346-21351, June 14, 2002
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From the University Laboratory of Physiology, Parks Road,
Oxford, OX1 3PT, United Kingdom
The precise molecular identity of the renal
ATP-regulated secretory K+ channel is still a matter
of some controversy. The inwardly rectifying K+ channel,
Kir1.1 (ROMK) appears to form the pore of the channel, and mutations in
Kir1.1 are responsible for Bartter syndrome. The native channel is
sensitive to inhibition by the sulfonylurea glibenclamide, and it has
been proposed that an accessory protein is required to confer
glibenclamide sensitivity to Kir1.1. Several recent studies have
suggested that the native channel is composed of the splice variant
Kir1.1b (ROMK2) and the sulfonylurea receptor isoform SUR2B and that
there is a direct physical interaction between these subunits. In this
study, we have monitored the interaction between Kir1.1b and SUR2B. We
find that SUR2B reaches the plasma membrane when coexpressed with
Kir6.1 or Kir6.2 but not when coexpressed with Kir1.1b. Furthermore, we
find that Kir1.1b exhibits an intrinsic sensitivity to inhibition by
glibenclamide with an affinity similar to the native channel. These
results demonstrate that SUR2B does not traffic to the membrane in the
presence of Kir1.1b and is not required to confer glibenclamide
sensitivity to Kir1.1b. This has important implications for the
presumed structure of the renal ATP-regulated secretory
K+ channel.
Intrinsic Sensitivity of Kir1.1 (ROMK) to Glibenclamide in the
Absence of SUR2B
IMPLICATIONS FOR THE IDENTITY OF THE RENAL ATP-REGULATED
SECRETORY K+ CHANNEL*
*
This work was supported by grants from the National Kidney
Research Fund and the Wellcome Trust.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.
A Royal Society University Research Fellow. To whom correspondence
should be addressed. E-mail: stephen.tucker@physiol.ox.ac.uk.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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