Cho, H Hwang, JY Kim, D Shin, HS Kim, Y Earm, YE Ho, WK 2024-01-21T10:10:08Z 2024-01-21T10:10:08Z 2021-09-01 2002-08-02 0021-9258 https://pubs.kist.re.kr/handle/201004/139292 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. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC DEPENDENT DESENSITIZATION ACTIVATION RECEPTORS CHANNELS INHIBITION HYDROLYSIS BETA(1) PIP2 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 Article 10.1074/jbc.M203660200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.31, pp.27742 - 27747 JOURNAL OF BIOLOGICAL CHEMISTRY 277 31 27742 27747 scie scopus 000177189800022 2-s2.0-0037008744 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article DEPENDENT DESENSITIZATION ACTIVATION RECEPTORS CHANNELS INHIBITION HYDROLYSIS BETA(1) PIP2