IRP3: KCNQ (Kv7) channel turnover and cellular excitability

KCNQ(KV7)基因编码电压门控钾(Kv)通道的ct亚基。KV7通道可在负膜电位时激活或缓慢失活，即在动作电位放电的亚阈值电位范围内。因此，KV7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因素。KCNQ基因突变可能与通道病变有关，如长QT综合征、BFNC、新生儿惊厥的良性ƒ或耳聋。许多与疾病相关的突变显然会影响KV7通道的贩运。KV7通道的一个特点是它们与钙调蛋白紧密结合。钙调蛋白与KV7亚单位的C末端结构域(S)的结合似乎是KV7活性通道组装和转运到质膜上所必需的。与LQTS或BFNC相关的KV7钙调蛋白结合位点的突变在体外导致质膜上活跃的KV7通道数量减少。根据以前的研究，我们假设刺激GαQ/11偶联受体可调节KV7通道的翻转，这与神经元兴奋性的短期和长期变化有关。

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.