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J Biol Chem. 2002 Aug 2;277(31):27742-7. Epub 2002 May 17.

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.

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  • 1National Research Laboratory for Cellular Signaling and Department of Physiology and Biophysics, Seoul National University College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul 110-799, Korea.

Abstract

Depletion of phosphatidylinositol 4,5-bisphosphate (PIP(2)) 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 PIP(2) 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 PIP(2) depletion, replenishment of PIP(2) was blocked by wortmannin. Wortmannin did not affect the desensitization and the recovery from desensitization. These results suggest that PIP(2) 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 PIP(2) to act as a signaling molecule.

PMID:
12019267
[PubMed - indexed for MEDLINE]
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