A激酶锚定蛋白150信号复合体促进毒蕈碱激动剂对M电流的抑制。
AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists.
作者信息
Hoshi Naoto, Zhang Jia-Sheng, Omaki Miho, Takeuchi Takahiro, Yokoyama Shigeru, Wanaverbecq Nicolas, Langeberg Lorene K, Yoneda Yukio, Scott John D, Brown David A, Higashida Haruhiro
机构信息
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
出版信息
Nat Neurosci. 2003 Jun;6(6):564-71. doi: 10.1038/nn1062.
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.
M型（KCNQ2/3）钾通道受G（q/11）偶联受体激活的抑制，从而增加神经元兴奋性。我们在此表明，大鼠KCNQ2可直接与多价A激酶锚定蛋白AKAP150结合。阻断AKAP150与KCNQ2通道复合物结合的肽可拮抗毒蕈碱对电流的抑制作用。一种无法结合蛋白激酶C（PKC）的AKAP150突变体形式AKAP（ΔA），也减弱了激动剂诱导的电流抑制。对重组KCNQ2通道的分析表明，通过与AKAP150结合来靶向PKC对这种抑制作用很重要。毒蕈碱刺激可增加KCNQ2通道的磷酸化；与AKAP（ΔA）共表达或用与二酰基甘油竞争的PKC抑制剂预处理均可阻止这种增加。这些抑制剂也减少了毒蕈碱对M电流的抑制作用。我们的数据表明，与AKAP150结合的PKC参与了受体诱导的M电流抑制。
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