Abstract
M-type (KCNQ2/3) potassium channels are suppressed by activation of G(q/11)-coupled receptors, thereby increasing neuronal excitability. We show here that rat KCNQ2 can bind directly to the multivalent A-kinase-anchoring protein AKAP150. Peptides that block AKAP150 binding to the KCNQ2 channel complex antagonize the muscarinic inhibition of the currents. A mutant form of AKAP150, AKAP(DeltaA), which is unable to bind protein kinase C (PKC), also attenuates the agonist-induced current suppression. Analysis of recombinant KCNQ2 channels suggests that targeting of PKC through association with AKAP150 is important for the inhibition. Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. Our data indicate that AKAP150-bound PKC participates in receptor-induced inhibition of the M-current.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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A Kinase Anchor Proteins
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Adaptor Proteins, Signal Transducing*
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Animals
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Carrier Proteins / drug effects
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Cells, Cultured
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Diglycerides / antagonists & inhibitors
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Diglycerides / metabolism
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Enzyme Inhibitors / pharmacology
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Ganglia, Sympathetic / drug effects
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Ganglia, Sympathetic / metabolism
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KCNQ2 Potassium Channel
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Macromolecular Substances
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Muscarinic Agonists / pharmacology
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Mutation / genetics
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neurons / drug effects
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Neurons / metabolism*
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Peptide Fragments / pharmacology
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Phosphorylation / drug effects
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Potassium Channels / drug effects
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Potassium Channels / metabolism*
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Potassium Channels, Voltage-Gated
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Protein Binding / drug effects
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Protein Binding / physiology
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Protein Isoforms / genetics
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Protein Isoforms / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Rats
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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A Kinase Anchor Proteins
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Adaptor Proteins, Signal Transducing
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Akap5 protein, rat
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Carrier Proteins
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Diglycerides
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Enzyme Inhibitors
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KCNQ2 Potassium Channel
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Kcnq2 protein, rat
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Macromolecular Substances
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Muscarinic Agonists
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Peptide Fragments
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Protein Isoforms
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Protein Kinase C