Carr David B, Day Michelle, Cantrell Angela R, Held Joshua, Scheuer Todd, Catterall William A, Surmeier D James
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Neuron. 2003 Aug 28;39(5):793-806. doi: 10.1016/s0896-6273(03)00531-2.
Voltage-gated Na+ channels are major targets of G protein-coupled receptor (GPCR)-initiated signaling cascades. These cascades act principally through protein kinase-mediated phosphorylation of the channel alpha subunit. Phosphorylation reduces Na+ channel availability in most instances without producing major alterations of fast channel gating. The nature of this change in availability is poorly understood. The results described here show that both GPCR- and protein kinase-dependent reductions in Na+ channel availability are mediated by a slow, voltage-dependent process with striking similarity to slow inactivation, an intrinsic gating mechanism of Na+ channels. This process is strictly associated with neuronal activity and develops over seconds, endowing neurons with a novel form of cellular plasticity shaping synaptic integration, dendritic electrogenesis, and repetitive discharge.
电压门控性钠离子通道是G蛋白偶联受体（GPCR）启动的信号级联反应的主要靶点。这些级联反应主要通过蛋白激酶介导的通道α亚基磷酸化发挥作用。在大多数情况下，磷酸化会降低钠离子通道的可用性，而不会对快速通道门控产生重大改变。这种可用性变化的本质尚不清楚。此处描述的结果表明，GPCR和蛋白激酶依赖性的钠离子通道可用性降低是由一个缓慢的、电压依赖性过程介导的，该过程与缓慢失活（钠离子通道的一种内在门控机制）具有惊人的相似性。这个过程与神经元活动密切相关，在数秒内发展，赋予神经元一种新型的细胞可塑性，从而塑造突触整合、树突电活动和重复放电。
