IRP3: KCNQ (Kv7) channel turnover and cellular excitability

IRP3：KCNQ (Kv7) 通道转换和细胞兴奋性

• 批准号: 45503360
• 负责人: Professor Dr. Olaf Pongs
• 金额: --
• 依托单位: Fachrichtung Physiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/45503360?language=en
• 关键词: IRP3; KCNQ; Kv7; channel; turnover

KCNQ (Kv7) genes encode ct-subunits of voltage-gated potassium (Kv) channels. Kv7 channels may activate and slowly deactivate at negative membrane potentials, i.e. in the subthreshold potential-range of action-potential firing. Kv7 channels, therefore, may be major players in controlling membrane resting potentials and/or action potential firing frequencies in excitable cells. Mutations in KCNQ genes may be associated with channelopathies such as the long QT syndrome (LQTS), BFNC, a benignƒorm of neonatal convulsions, or deafness. Many of the disease-related mutations affect apparently Kv7 channel trafficking. A hallmark of Kv7 channels is their tight association with calmodulin. The binding of calmodulin to C-terminal domain(s) of Kv7 subunit appears essential for assembly and trafficking of active Kv7 channels to the plasma membrane. Mutations in the Kv7 calmodulin binding site that are associated with LQTS or BFNC cause in vitro a reduced number of active Kv7 channels in the plasma membrane. Based on previous studies we hypothesize that stimulation of Gαq/11-coupled receptors modulates Kv7 channel turnover associated with short- and long-term changes in neuronal excitability.

KCNQ（KV7）基因编码电压门控钾（KV）通道的CT-subunits。 KV7通道可能会在负膜电位上激活并缓慢停用，即在子阈值的动作触发触发范围内。因此，KV7通道可能是控制膜静息电势和/或动作电势发射频率的主要参与者。 KCNQ基因中的突变可能与通道病有关，例如长QT综合征（LQTS），BFNC，NeonaTal Shemignal chomignƒ新生儿抽搐或死亡。许多与疾病相关的突变显然影响了KV7通道贩运。 KV7频道的标志是他们与钙调蛋白的紧密联系。钙调蛋白与KV7亚基的C末端结构域的结合对于组装和运输活跃的KV7通道与质膜的结合似乎至关重要。与LQT或BFNC相关的KV7钙调蛋白结合位点的突变导致质膜中减少活性KV7通道的数量减少。根据先前的研究，我们假设刺激GαQ/11偶联受体会调节与神经元令人兴奋的短期和长期变化相关的KV7通道更新。