ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C
ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C
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DOI：
10.1016/s0896-6273(03)00256-3
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发表时间：
2003-05-08
期刊：
影响因子：
16.2
通讯作者：
Jan, LY
中科院分区：
文献类型：
--
作者：
Hu, KL;Huang, CS;Jan, LY
ATP 敏感钾 (K-ATP) 通道在代谢应激下激活，以保护神经元和心肌细胞。然而，过度的通道激活可能会导致心脏心律失常并使大脑中的神经元沉默。在这里，我们报告说，PKC 介导的 K-ATP 通道数量下调，通过动力依赖性通道内化，可以作为控制 K-ATP 激活的制动机制。 K-ATP 孔内衬 Kir6.2 亚基中的双亮氨酸基序，但不是用于通道激活的 PKC 磷酸化位点，对于 PKC 下调至关重要。尽管 K-ATP 激活会导致代谢受抑制的心室肌细胞的动作电位持续时间 (APD) 迅速缩短，但腺苷受体刺激和随后的 PKC 介导的 K-ATP 通道内化可以起到制动作用，以减轻这种 APD 缩短。同样，在代谢应激下的海马 CA1 神经元中，PKC 介导的、动力依赖性 K-ATP 通道内化也可以充当制动器，抑制 K-ATP 激活导致的兴奋性快速下降。
ATP-sensitive potassium (K-ATP) channels activate under metabolic stress to protect neurons and cardiac myocytes. However, excessive channel activation may cause arrhythmia in the heart and silence neurons in the brain. Here, we report that PKC-mediated downregulation of K-ATP channel number, via dynamin-dependent channel internalization, can act as a brake mechanism to control K-ATP activation. A dileucine motif in the pore-lining Kir6.2 subunit of K-ATP, but not the site of PKC phosphorylation for channel activation, is essential for PKC downregulation. Whereas K-ATP activation results in a rapid shortening of the action potential duration (APD) in metabolically inhibited ventricular myocytes, adenosine receptor stimulation and consequent PKC-mediated K-ATP channel internalization can act as a brake to lessen this APD shortening. Likewise, in hippocampal CA1 neurons under metabolic stress, PKC-mediated, dynamin-dependent K-ATP channel internalization can also act as a brake to dampen the rapid decline of excitability due to K-ATP activation.