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亚基。Kv7通道可能在负膜电位，即在动作电位放电的阈下电位范围内激活和缓慢失活。因此，Kv7通道可能是控制可兴奋细胞的膜静息电位和/或动作电位发射频率的主要参与者。KCNQ基因突变可能与通道病变有关，如长QT综合征（LQTS）、BFNC、benignƒorm新生儿惊厥或耳聋。许多与疾病相关的突变明显影响Kv7通道的运输。Kv7通道的一个特点是它们与钙调蛋白紧密相关。钙调蛋白与Kv7亚基c端结构域的结合对于活性Kv7通道的组装和转运到质膜至关重要。在体外实验中，与LQTS或BFNC相关的Kv7钙调素结合位点的突变导致质膜中活性Kv7通道的数量减少。基于以往的研究，我们假设g- αq/11偶联受体的刺激可调节与神经元兴奋性短期和长期变化相关的Kv7通道转换。