Unidad de Biofísica, Consejo Superior de Investigaciones Científicas-Universidad del País Vasco/Euskal Herriko Unibersitatea, Leioa, Spain.
PLoS One. 2011;6(9):e25508. doi: 10.1371/journal.pone.0025508. Epub 2011 Sep 28.
M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.
M 通道是电压门控钾通道，由 Kv7.2-7.5 亚基组成，它们是神经元兴奋性的重要调节剂。钙调蛋白结合对于 Kv7 通道功能是必需的，而 Kv7.2 中的突变破坏了钙调蛋白结合，导致良性家族性新生儿惊厥（BFNC），这是一种显性遗传性人类癫痫。基于钙调蛋白结合缺陷的 Kv7.2 突变体没有功能，钙调蛋白已被定义为 Kv7 通道的辅助亚基。然而，我们已经确定了一个假定的磷酸模拟突变 S511D，它允许钙调蛋白独立的功能。因此，我们的数据表明，钙调蛋白的组成性固定不需要 Kv7 通道功能。
