AKAP79/150 signal complexes in G-protein modulation of neuronal ion channels

Jie Zhang, Manjot Bal, Sonya Bierbower, Oleg Zaika, Mark S. Shapiro

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Voltage-gated M-type (KCNQ) K+ channels play critical roles in regulation of neuronal excitability. Previous work showed A-kinaseanchoring protein (AKAP)79/150-mediated protein kinase C (PKC) phosphorylation of M channels to be involved in M current (IM) suppression by muscarinic M1, but not bradykinin B2, receptors. In this study, we first explored whether purinergic and angiotensin suppression of IM in superior cervical ganglion (SCG) sympathetic neurons involves AKAP79/150. Transfection into rat SCG neurons of ΔA-AKAP79, which lacks the A domain necessary for PKC binding, or the absence of AKAP150 in AKAP150-/- mice, did not affect IM suppression by purinergic agonist or by bradykinin, but reduced IM suppression by muscarinic agonist and angiotensin II. Transfection of AKAP79, but not ΔA-AKAP79 or AKAP15, rescued suppression of IM by muscarinic receptors in AKAP150-/-neurons. We also tested association of AKAP79 with M1, B2, P2Y6, and AT1 receptors, and KCNQ2 and KCNQ3 channels, via Förster resonance energy transfer (FRET) on Chinese hamster ovary cells under total internal refection fluorescence microscopy, which revealed substantial FRET between AKAP79 and M1 or AT1 receptors, and with the channels, but only weak FRET with P2Y6 or B2 receptors. The involvement of AKAP79/150 in Gq/11-coupled muscarinic regulation of N- and L-type Ca2+ channels and by cAMP/protein kinase A was also studied. We found AKAP79/150 to not play a role in the former, but to be necessary for forskolin-induced upregulation of L-current. Thus, AKAP79/150 action correlates with the PIP2 (phosphatidylinositol 4,5-bisphosphate)-depletion mode of IM suppression, but does not generalize to Gq/11-mediated inhibition of N- or L-type Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)7199-7211
Number of pages13
JournalJournal of Neuroscience
Issue number19
StatePublished - May 11 2011

ASJC Scopus subject areas

  • Neuroscience(all)


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