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- W2063345490 abstract "A-kinase-anchoring protein (AKAP)79/150 mediated PKC phosphorylation of M-type (KCNQ) channels is involved in M current (IM) suppression by muscarinic M1, but not bradykinin B2 receptors (Hoshi et al. Nat. Cell Biol. 7:1066-73). In this study, we first explored the involvement of AKAP79/150 in muscarinic suppression of KCNQ currents by co-transfecting AKAP79 with KCNQ1-5 subunits in CHO cells stably expressing M1 receptors. Expression of AKAP79 sensitized KCNQ2-5 and KCNQ2/3, but not KCNQ1, channels to suppression by the M1 receptor agonist oxotremorine (oxo-M). Mutation of the PKC phosphorylation site on KCNQ4 (T553A) eliminated the effect of AKAP79, confirming the role of PKC. Co-transfection of wild-type, but not dominant negative, calmodulin abolished the effect of AKAP79 on KCNQ2/3 channels. We asked if purinergic and angiotensin suppression of IM in superior cervical ganglion (SCG) sympathetic neurons involves AKAP79/150, since purinergic P2Y receptors depress IM in SCG neurons via a similar mechanism to that of bradykinin, involving IP3-mediated Ca2+ signals, whereas angiotensin AT1 receptors depress IM via a similar mechanism as M1 receptors, by depletion of PIP2. Transfection of ΔA-AKAP79, which lacks the A-domain necessary for PKC binding, did not affect IM suppression by the purinergic agonist UTP (2 μM), nor by bradykinin (100 nM), but did reduce IM suppression by oxo-M (1 μM) and angiotensin II (500 nM). We also tested association of AKAP79 with M1, B2, P2Y6 and AT1 receptors via FRET experiments on CHO cells under TIRF microscopy, which revealed weaker FRET between AKAP79 and P2Y6 or B2 receptors than for M1 and AT1 receptors. Our data suggest AKAP79/150 action generalizes to KCNQ2-5 subtypes, is disrupted by calmodulin, and is involved in angiotensin, but not in purinergic, suppression of neuronal M current. Supported by NIH grants R01 NS043394 and R01 NS065138." @default.
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- W2063345490 date "2010-01-01" @default.
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- W2063345490 title "Receptor and Subunit Specificity in AKAP79/150 Actions On M-Type(KCNQ) K+ Channels" @default.
- W2063345490 doi "https://doi.org/10.1016/j.bpj.2009.12.1144" @default.
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