IRP3: KCNQ (Kv7) channel turnover and cellular excitability

KCNQ（Kv 7）基因编码电压门控钾（Kv）通道的Ct亚基。Kv 7通道可以在负膜电位下激活和缓慢失活，即在动作电位放电的阈下电位范围内。因此，Kv 7通道可能是控制可兴奋细胞膜静息电位和/或动作电位放电频率的主要参与者。KCNQ基因突变可能与通道病如长QT综合征（LQTS）、BFNC、新生儿惊厥的良性病变或耳聋有关。许多疾病相关的突变明显影响Kv 7通道运输。Kv 7通道的一个标志是它们与钙调蛋白的紧密结合。钙调素与Kv 7亚基C-末端结构域的结合对于活性Kv 7通道的组装和运输至质膜是必不可少的。与LQTS或BFNC相关的Kv 7钙调蛋白结合位点的突变在体外导致质膜中活性Kv 7通道数量减少。基于先前的研究，我们假设刺激Gαq/11偶联受体调节与神经元兴奋性的短期和长期变化相关的Kv 7通道转换。

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.