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J. Biol. Chem., Vol. 276, Issue 1, 159-164, January 5, 2001
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From the National Research Laboratory for Cellular Signalling and
Department of Physiology & Biophysics, Seoul National University
College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul 110-799, Korea
and the We have investigated the effect of
Phosphatidylinositol 4,5-Bisphosphate Is Acting as a Signal
Molecule in
1-Adrenergic Pathway via the Modulation of
Acetylcholine-activated K+ Channels in Mouse Atrial
Myocytes*
, Department of Internal Medicine, Asan Medical
Center, Seoul 138-140, Korea
1-adrenergic agonist phenylephrine (PE) on
acetylcholine-activated K+ currents
(IKACh). IKACh was
recorded in mouse atrial myocytes using the patch clamp technique.
IKACh was activated by 10 µM ACh
and the current decreased by 44.27 ± 2.38% (n = 12) during 4 min due to ACh-induced desensitization. When PE was
applied with ACh, the extent of desensitization was markedly increased to 69.34 ± 2.22% (n = 9), indicating the
presence of PE-induced desensitization. IKACh
was fully recovered from desensitization after a 6-min washout.
PE-induced desensitization of IKACh was not
affected by protein kinase C inhibitor, calphostin C, but abolished by
phospholipase C (PLC) inhibitor, neomycin. When phophatidylinositol 4,5-bisphosphate (PIP2) replenishment was blocked by
wortmannin (an inhibitor of phophatidylinositol 3-kinase and
phophatidylinositol 4-kinase), desensitization of
IKACh in the presence of PE was further
increased (97.25 ± 7.63%, n = 6). Furthermore,
the recovery from PE-induced desensitization was inhibited, and the
amplitude of IKACh at the second exposure after
washout was reduced to 19.65 ± 2.61% (n = 6) of
the preceding level. These data suggest that the KACh
channel is modulated by PE through PLC stimulation and depletion of
PIP2.
*
This work was supported by BK21 Human Life Sciences and the
Korean Research Foundation (KRF, 1999-015-FP0035).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.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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