Neuronal activity leads to an increase in local cerebral blood flow (CBF) to allow adequate supply of oxygen and nutrients to active neurons, a process termed neurovascular coupling (NVC). We have previously shown that capillary endothelial cell (cEC) inwardly rectifying K⁺ (Kir) channels can sense neuronally evoked increases in interstitial K⁺ and induce rapid and robust dilations of upstream parenchymal arterioles, suggesting a key role of cECs in NVC. The requirements of this signal conduction remain elusive. Here, we utilize mathematical modeling to investigate how small outward currents in stimulated cECs can elicit physiologically relevant spread of vasodilatory signals within the highly interconnected brain microvascular network to increase local CBF. Our model shows that the Kir channel can act as an “on–off” switch in cECs to hyperpolarize the cell membrane as extracellular K⁺ increases. A local hyperpolarization can be amplified by the voltage-dependent activation of Kir in neighboring cECs. Sufficient Kir density enables robust amplification of the hyperpolarizing stimulus and produces responses that resemble action potentials in excitable cells. This Kir-mediated excitability can remain localized in the stimulated region or regeneratively propagate over significant distances in the microvascular network, thus dramatically increasing the efficacy of K⁺ for eliciting local hyperemia. Modeling results show how changes in cEC transmembrane current densities and gap junctional resistances can affect K⁺-mediated NVC and suggest a key role for Kir as a sensor of neuronal activity and an amplifier of retrograde electrical signaling in the cerebral vasculature.

神经元活动导致局部脑血流量 (CBF) 增加，从而为活跃的神经元提供充足的氧气和营养，这一过程称为神经血管耦合 (NVC)。我们之前已经表明，毛细血管内皮细胞 (cEC) 向内整流 K ⁺ (Kir) 通道可以感知神经元诱发的间质 K ^+增加并诱导上游实质小动脉快速而强劲的扩张，表明 cEC 在 NVC 中的关键作用。这种信号传导的要求仍然难以捉摸。在这里，我们利用数学模型来研究受刺激的 cEC 中的小外向电流如何在高度互连的脑微血管网络中引起血管舒张信号的生理相关传播，以增加局部 CBF。我们的模型表明，Kir 通道可以作为 cEC 中的“开关”开关，将细胞膜超极化为细胞外 K ⁺增加。局部超极化可以通过邻近 cEC 中 Kir 的电压依赖性激活来放大。足够的 Kir 密度能够使超极化刺激得到稳健的放大，并产生类似于可兴奋细胞中动作电位的反应。这种 Kir 介导的兴奋性可以保持在受刺激区域内，或者在微血管网络中的显着距离上再生传播，从而显着提高 K ⁺引起局部充血的功效。建模结果显示 cEC 跨膜电流密度和间隙连接电阻的变化如何影响 K ⁺介导的 NVC，并表明 Kir 在脑血管系统中作为神经元活动传感器和逆行电信号放大器的关键作用。