Acetylcholine-induced phosphatidylinositol 4,5-bisphosphate depletion does not cause short-term desensitization of G protein-gated inwardly rectifying K+ current in mouse atrial myocytes

Authors
Cho, HHwang, JYKim, DShin, HSKim, YEarm, YEHo, WK
Issue Date
2002-08-02
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.31, pp.27742 - 27747
Abstract
Depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) induced by phenylephrine or endothelin causes the inhibition of acetylcholine-activated K+ current (I-KACh) in atrial myocytes. In the present study, we have investigated the hypothesis that muscarinic receptor induced PIP2 depletion also causes inhibition of I-KACh, resulting in desensitization. We confirmed the expression of G(q)-coupled muscarinic receptors in mouse atrial myocytes using reverse transcriptase-polymerase chain reaction. The involvement of M-1 and M-3 receptors in desensitization is examined using specific antagonists, 4-DAMP and pirenzepine, but they significantly reduced peak I-KACh, implying nonspecific M-2 blockade. When ACh-induced phosphoinositide depletion was specifically inhibited using PLCbeta1 knock-out mice, the extent of desensitization during 4 min was 47.5 +/- 3.2%, which was not different from that in wild type (46.8 +/- 2.1%). Phenylephrine-induced phosphoinositide hydrolysis and phenylephrine-induced inhibition of I-KACh were not affected by PLCbeta1 knock-out. To facilitate PIP2 depletion, replenishment of PIP2 was blocked by wortmannin. Wortmannin did not affect the desensitization and the recovery from desensitization. These results suggest that PIP2 depletion by acetylcholine does not contribute to short-term desensitization of I-KACh. The differential regulation of I-KACh by different phospholipase C-linked receptors may imply that receptor co-localization is required for PIP2 to act as a signaling molecule.
Keywords
DEPENDENT DESENSITIZATION; ACTIVATION; RECEPTORS; CHANNELS; INHIBITION; HYDROLYSIS; BETA(1); PIP2; DEPENDENT DESENSITIZATION; ACTIVATION; RECEPTORS; CHANNELS; INHIBITION; HYDROLYSIS; BETA(1); PIP2
ISSN
0021-9258
URI
https://pubs.kist.re.kr/handle/201004/139292
DOI
10.1074/jbc.M203660200
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KIST Article > 2002
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