Centre for Bioengineering, University of Canterbury, New Zealand; Van der Veer Institute for Parkinson's and Brain Research, Christchurch, New Zealand.
J Theor Biol. 2011 Oct 7;286(1):13-23. doi: 10.1016/j.jtbi.2011.07.006. Epub 2011 Jul 20.
Functional hyperemia is an important metabolic autoregulation mechanism by which increased neuronal activity is matched by a rapid and regional increase in blood supply. This mechanism is facilitated by a process known as "neurovascular coupling"--the orchestrated communication system involving neurons, astrocytes and arterioles. Important steps in this process are the production of EETs in the astrocyte and the release of potassium, via two potassium channels (BK and KIR), into the perivascular space. We provide a model which successfully accounts for several observations seen in experiment. The model is capable of simulating the approximate 15% arteriolar dilation caused by a 60-s neuronal activation (modelled as a release of potassium and glutamate into the synaptic cleft). This model also successfully emulates the paradoxical experimental finding that vasoconstriction follows vasodilation when the astrocytic calcium concentration (or perivascular potassium concentration) is increased further. We suggest that the interaction of the changing smooth muscle cell membrane potential and the changing potassium-dependent resting potential of the KIR channel are responsible for this effect. Finally, we demonstrate that a well-controlled mechanism of potassium buffering is potentially important for successful neurovascular coupling.
功能充血是一种重要的代谢自动调节机制，通过该机制，神经元活动的增加与血液供应的快速和区域增加相匹配。这种机制是通过一种称为“神经血管偶联”的过程来促进的，即涉及神经元、星形胶质细胞和小动脉的协调通信系统。该过程中的重要步骤包括在星形胶质细胞中产生 EETs，以及通过两种钾通道（BK 和 KIR）将钾释放到血管周围空间。我们提供了一个模型，该模型成功地解释了实验中观察到的几个现象。该模型能够模拟由 60 秒神经元激活（模拟为钾和谷氨酸释放到突触间隙）引起的约 15%的小动脉扩张。该模型还成功地模拟了一个矛盾的实验发现，即当星形胶质细胞内钙离子浓度（或血管周围钾浓度）进一步增加时，血管收缩紧随血管扩张。我们认为，平滑肌细胞膜电位的变化和 KIR 通道的钾依赖性静息电位的变化之间的相互作用是造成这种效应的原因。最后，我们证明了钾缓冲的良好控制机制对成功的神经血管偶联可能很重要。
