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Originally published In Press as doi:10.1074/jbc.M105572200 on August 27, 2001
J. Biol. Chem., Vol. 276, Issue 44, 40811-40816, November 2, 2001
Different Subtypes of 1-Adrenoceptor Modulate
Different K+ Currents via Different Signaling Pathways in
Canine Ventricular Myocytes*
Huizhen
Wang §¶,
Baofeng
Yang¶ ,
Yiqiang
Zhang ,
Hong
Han **,
Jingxiong
Wang ,
Hong
Shi , and
Zhiguo
Wang  §§
From the Research Center, Montreal Heart Institute,
Montreal, Quebec H1T 1C8, Canada, the
 Department of Medicine, University of
Montreal, Montreal, Quebec H3C 3J7, Canada, and the Department
of Pharmacology, Harbin Medical University, Harbin, Heilongjiang
150086, China
Multiple subtypes ( 1A,
1B, and 1D) of
1-adrenoreceptors ( 1ARs) co-exist in the
heart and mediate a variety of cellular functions. We studied
1AR modulation of inward rectifier
(IK1) and transient outward
(Ito) K+ currents in canine
ventricular myocytes. Phenylephrine at 10 µM depressed
only Ito without affecting
IK1 and at 100 µM inhibited both
Ito and IK1. The effect
of phenylephrine on Ito was abolished by
(+)niguldipine (10 nM) to inhibit 1AARs but
not by chloroethyclonidine (10 µM) to inactivate
1BARs nor by BMY-7378 to antagonize
1DARs. In contrast, phenylephrine inhibition of
IK1 was reversed only by BMY-7378 (1 nM). PDD (100 nM, phorbol ester activator of
protein kinase C (PKC)) simulates and bisindolylmaleimide (50 nM, PKC inhibitor) weakens phenylephrine modulation of
Ito but not IK1. Ca2+/calmodulin-dependent protein kinase II
(CaMKII) inhibitor KN-93 and inhibitor peptides abolished the effects
of phenylephrine on IK1. Enhancement of PKC or
CaMKII activities was seen in 1aAR- or
1dAR-transfected HEK293 cells and in myocytes pretreated
with 10 or 100 µM phenylephrine, respectively. Our data
suggest that different subtypes of 1ARs selectively
modulate different cardiac K+ currents via different signal
transduction mechanisms; 1AARs mediate
Ito regulation via PKC, and
1DARs mediate IK1 regulation via
CaMKII.
*
This work was supported in part by funds from the Canadian
Institute of Health Research, the Heart and Stroke Foundation of Quebec, and the Fonds de la Recherche de l'Institut de Cardiologie de
Montreal (to Z. 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.
§
Research fellow of the Canadian Institute of Health Research.
¶
These authors contributed equally to this work.
**
Research fellow of the Heart and Stroke Foundation of Canada.
§§
Research scholar of the Heart and Stroke Foundation of Canada.
To whom correspondence should be addressed: Research Center, Montreal Heart Inst., 5000 Belanger East, Montreal, PQ H1T 1C8, Canada.
Tel.: 514-376-3330; Fax: 514-376-1355; E-mail:
wangz@icm.umontreal.ca.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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