Basic Sciences, Loma Linda University, Loma Linda, California, USA.
Microcirculation. 2023 Jan;30(1):e12797. doi: 10.1111/micc.12797. Epub 2023 Jan 6.
Endothelial cell (EC) coupling occurs through gap junctions and underlies cerebral blood flow regulation governed by inward-rectifying K (K ) channels. This study addressed effects of K channel activity on EC coupling before and during Alzheimer's disease (AD).
Intact EC tubes (width: ~90-100 μm; length: ~0.5 mm) were freshly isolated from posterior cerebral arteries of young Pre-AD (1-3 months) and aged AD (13-18 months) male and female 3xTg-AD mice. Dual intracellular microelectrodes applied simultaneous current injections (±0.5-3 nA) and membrane potential (V ) recordings in ECs at distance ~400 μm. Elevated extracellular potassium ([K ] ; 8-15 mmol/L; reference, 5 mmol/L) activated K channels.
Conducted V (∆V ) responses ranged from -30 to 30 mV in response to -3 to +3 nA (linear regression, R ≥ .99) while lacking rectification for charge polarity or axial direction of spread. Conduction slope decreased ~10%-20% during 15 mmol/L [K ] in Pre-AD males and AD females. 15 mmol/L [K ] decreased conduction by ~10%-20% at lower ∆V thresholds in AD animals (±20 mV) versus Pre-AD (~±25 mV). AD increased conducted hyperpolarization by ~10%-15% during 8-12 mmol/L [K ] .
Brain endothelial K channel activity modulates bidirectional spread of vasoreactive signals with enhanced regulation of EC coupling during AD pathology.
内皮细胞（EC）通过缝隙连接偶联，其基础是内向整流钾（K ）通道控制的脑血流调节。本研究探讨了 K 通道活性对 AD 前和 AD 期间 EC 偶联的影响。
从年轻的 Pre-AD（1-3 个月）和老年 AD（13-18 个月）雄性和雌性 3xTg-AD 小鼠的大脑后动脉中新鲜分离完整的 EC 管（宽度：90-100μm；长度：0.5mm）。双细胞内微电极同时施加电流注入（±0.5-3nA）和距离~400μm 的 EC 膜电位（V ）记录。升高细胞外钾浓度（[K ]；8-15mmol/L；对照，5mmol/L）激活 K 通道。
-3 至+3nA （线性回归，R ≥ .99）的响应时，传导 V （∆V ）响应范围为-30 至 30mV，而对电荷极性或轴向传播方向没有整流。在 Pre-AD 雄性和 AD 雌性中，15mmol/L [K ] 时，传导斜率下降了10%-20%。在 AD 动物（±20mV）中，15mmol/L [K ] 降低了较低 ∆V 阈值下的传导10%-20%（±25mV）。AD 在 8-12mmol/L [K ] 期间增加了10%-15%的传导超极化。
大脑内皮 K 通道活性调节血管反应性信号的双向传播，在 AD 病理过程中增强了 EC 偶联的调节。
