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Phosphatidylinositol 4,5-Bisphosphate Is Acting as a Signal Molecule in α1-Adrenergic Pathway via the Modulation of Acetylcholine-activated K+Channels in Mouse Atrial Myocytes*
- Source :
- Journal of Biological Chemistry; January 2001, Vol. 276 Issue: 1 p159-164, 6p
- Publication Year :
- 2001
-
Abstract
- We have investigated the effect of α1-adrenergic agonist phenylephrine (PE) on acetylcholine-activated K+currents (IKACh). IKAChwas recorded in mouse atrial myocytes using the patch clamp technique.IKAChwas activated by 10 μmACh 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. IKAChwas fully recovered from desensitization after a 6-min washout. PE-induced desensitization of IKAChwas 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 IKAChin 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 IKAChat the second exposure after washout was reduced to 19.65 ± 2.61% (n= 6) of the preceding level. These data suggest that the KAChchannel is modulated by PE through PLC stimulation and depletion of PIP2.
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Volume :
- 276
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs7164443
- Full Text :
- https://doi.org/10.1074/jbc.M004826200