Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels.
The second messenger for closure of M/KCNQ potassium channels in post-ganglionic neurons and central neurons had remained as a 'mystery in the neuroscience field' for over 25 years. However, recently the details of the pathway leading from muscarinic acetylcholine receptor (mAChR)-stimulation to suppression of the M/KCNQ-current were discovered. A key molecule is A-kinase anchoring protein (AKAP; AKAP79 in human, or its rat homolog, AKAP150) which forms a trimeric complex with protein kinase C (PKC) and KCNQ channels. AKAP79 or 150 serves as an adapter that brings the anchored C-kinase to the substrate KCNQ channel to permit the rapid and 'definitive' phosphorylation of serine residues, resulting in avoidance of signal dispersion. Thus, these findings suggest that mAChR-induced short-term modulation (or memory) does occur within the already well-integrated molecular complex, without accompanying Hebbian synapse plasticity. However, before this identity is confirmed, many other modulators which affect M-currents remain to be addressed as intriguing issues.
Higashida
Haruhiro
H
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan. haruhiro@med.kanazawa-u.ac.jp
Hoshi
Naoto
N
Zhang
Jia-Sheng
JS
Yokoyama
Shigeru
S
Hashii
Minako
M
Jin
Duo
D
Noda
Mami
M
Robbins
Jon
J
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D051656:KCNQ Potassium Channels; D008954:Models, Biological; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D051656:KCNQ Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011976:Receptors, Muscarinic; D011493:Protein Kinase C