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J. Biol. Chem., Vol. 277, Issue 50, 48282-48288, December 13, 2002
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From the Department of Pharmacology, University of
Minnesota, Minneapolis, Minnesota 55455
The muscarinic-gated atrial potassium
(IKACh) channel contributes to the heart rate
decrease triggered by the parasympathetic nervous system.
IKACh is a heteromultimeric complex formed by Kir3.1 and
Kir3.4 subunits, although Kir3.4 homomultimers have also been proposed
to contribute to this conductance. While Kir3.4 homomultimers evince
many properties of IKACh, the contribution of Kir3.1 to
IKACh is less well understood. Here, we explored the
significance of Kir3.1 using knock-out mice. Kir3.1 knock-out mice were
viable and appeared normal. The loss of Kir3.1 did not affect the level
of atrial Kir3.4 protein but was correlated with a loss of
carbachol-induced current in atrial myocytes. Low level channel
activity resembling recombinant Kir3.4 homomultimers was observed in
40% of the cell-attached patches from Kir3.1 knock-out myocytes.
Channel activity typically ran down quickly, however, and was not
recovered in the inside-out configuration despite the addition of GTP
and ATP to the bath. Both Kir3.1 knock-out and Kir3.4 knock-out
mice exhibited mild resting tachycardias and blunted responses to
pharmacological manipulation intended to activate IKACh.
We conclude that Kir3.1 confers properties to IKACh
that enhance channel activity and that Kir3.4 homomultimers do not
contribute significantly to the muscarinic-gated potassium current.
Contribution of the Kir3.1 Subunit to the Muscarinic-gated Atrial
Potassium Channel IKACh*
*
This work was supported in part by National Institutes of
Health Grant RO1 MH61933 and a grant from the McKnight Foundation (to
K. W.).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 Pharmacology,
University of Minnesota, 6-120 Jackson Hall, 321 Church St. S.E.,
Minneapolis, MN 55455. Tel.: 612-624-5966; Fax: 612-625-8408; E-mail:
wickm002@tc.umn.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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