Expression of the voltage- and Ca2+-dependent BK potassium channel subunits BKβ1 and BKβ4 in rodent astrocytes.
Expression of the voltage- and Ca2+-dependent BK potassium channel subunits BKβ1 and BKβ4 in rodent astrocytes.
复制标题
电压和 Ca2 依赖性 BK 钾通道亚基 BKβ1 和 BKβ4 在啮齿动物星形胶质细胞中的表达。
作者：
Seidel,KatharinaN;Derst,Christian;Salzmann,Mikhail;Höltje,Markus;Priller,Josef;Markgraf,René;Heinemann,StefanH;Heilmann,Heike;Skatchkov,SergueiN;Eaton,MistyJ;Veh,RüdigerW;Prüss,Harald
大电导钙激活（BK）钾通道主要参与神经血管偶联、免疫和神经传递。被膜去极化、不同配体和细胞内Ca2+协同激活的能力将细胞内信号传导和膜兴奋性联系起来。BK通道的多种生理功能主要依赖于调节性β亚基。尽管最初的研究描述了BKβ亚基在啮齿动物脑中的神经元分布，但在很大程度上不知道哪些β亚基蛋白在星形胶质细胞中表达，从而介导这些调节作用。因此，我们分析了BKβ亚基在大鼠和小鼠脑和神经胶质细胞培养物中的表达。针对BKβ4通道亚基的单特异性多克隆抗体被提出，亲和纯化并广泛表征。在几个星形胶质细胞群体和培养细胞中检测到BKβ4和较少程度的BKβ1转录本和蛋白。在室管膜下区的星形胶质细胞祖细胞中检测到特别强的BKβ4免疫染色。BKα和BKβ4在星形胶质细胞中的重叠表达暗示了一种功能关系，并表明BKβ4是星形胶质细胞BK通道的重要辅助β亚基。此外，BKβ4可能发挥独立于α亚基的作用，因为Nav1.6和BKβ4的功能性异源共表达导致Nav1.6钠电流降低。因此，星形胶质细胞中的BKβ4表达可能参与调节星形胶质细胞电压梯度和维持K+稳态，从而使星形胶质细胞能够实现其对适当脑功能的复杂调节影响。© 2011 Wiley利斯公司
Large‐conductance Ca2+‐activated (BK) potassium channels are centrally involved in neurovascular coupling, immunity, and neural transmission. The ability to be synergistically activated by membrane depolarization, different ligands and intracellular Ca2+links intracellular signaling and membrane excitability. The diverse physiological functions of BK channels crucially depend on regulatory β subunits. Although first studies characterized the neuronal distribution of BKβ subunits in the rodent brain, it is largely unknown which β subunit proteins are expressed in astrocytes and thus mediate these regulatory effects. We therefore analyzed the expression of BKβ subunits in rat and mouse brain and glial cell cultures. A monospecific polyclonal antibody against the BKβ4 channel subunit was raised, affinity‐purified and extensively characterized. BKβ4 and to a lesser degree BKβ1 transcripts and protein were detected in several astrocytic populations and cultured cells. Particularly strong BKβ4 immunostaining was detected in astrocytic progenitors derived from the subventricular zone. The overlapping expression of BKα and BKβ4 in astrocytes implies a functional relationship and suggests that BKβ4 is an important accessory β subunit for astrocytic BK channels. In addition, BKβ4 might exert effects independent of the α subunit as functional heterologous co‐expression of Nav1.6 and BKβ4 resulted in reduced Nav1.6 sodium currents. Thus, BKβ4 expression in astrocytes likely participates in regulating astrocytic voltage gradients and maintaining K+homeostasis, hence enabling astrocytes to fulfill their complex regulatory influence on proper brain function. © 2011 Wiley‐Liss, Inc.