Regulation of neurovascular coupling in autoimmunity to water and ion channels.

Regulation of neurovascular coupling in autoimmunity to water and ion channels.

Much progress has been made in understanding autoimmune channelopathies, but the underlying pathogenic mechanisms are not always clear due to broad expression of some channel proteins. Recent studies show that autoimmune conditions that interfere with neurovascular coupling in the central nervous system (CNS) can lead to neurodegeneration. Cerebral blood flow that meets neuronal activity and metabolic demand is tightly regulated by local neural activity. This process of reciprocal regulation involves coordinated actions of a number of cell types, including neurons, glia, and vascular cells. In particular, astrocytic endfeet cover more than 90% of brain capillaries to assist blood-brain barrier (BBB) function, and wrap around synapses and nodes of Ranvier to communicate with neuronal activity. In this review, we highlight four types of channel proteins that are expressed in astrocytes, regarding their structures, biophysical properties, expression and distribution patterns, and related diseases including autoimmune disorders. Water channel aquaporin 4 (AQP4) and inwardly-rectifying potassium (Kir4.1) channels are concentrated in astrocytic endfeet, whereas some voltage-gated Ca2+ and two-pore-domain K+ channels are expressed throughout the cell body of reactive astrocytes. More channel proteins are found in astrocytes under normal and abnormal conditions. This research field will contribute to a better understanding of pathogenic mechanisms underlying autoimmune disorders.

在理解自身免疫性通道病方面已经取得了很大进展，但由于某些通道蛋白的广泛表达，潜在的致病机制并不总是清晰的。近期研究表明，干扰中枢神经系统（CNS）神经血管耦合的自身免疫状况可导致神经退行性变。满足神经元活动和代谢需求的脑血流受到局部神经活动的严格调控。这种相互调节的过程涉及多种细胞类型的协同作用，包括神经元、神经胶质细胞和血管细胞。特别是，星形胶质细胞的足突覆盖超过90%的脑毛细血管以协助血脑屏障（BBB）功能，并环绕突触和郎飞结与神经元活动进行信息交流。在这篇综述中，我们强调了在星形胶质细胞中表达的四种通道蛋白，包括它们的结构、生物物理特性、表达和分布模式，以及相关疾病，包括自身免疫性疾病。水通道蛋白4（AQP4）和内向整流钾（Kir4.1）通道集中在星形胶质细胞足突，而一些电压门控Ca2+通道和双孔钾通道在反应性星形胶质细胞的整个细胞体中表达。在正常和异常条件下，在星形胶质细胞中发现了更多的通道蛋白。这一研究领域将有助于更好地理解自身免疫性疾病的潜在致病机制。