A dynamic model of neurovascular coupling network accounting for capillary K+-sensing vasomotion

Abstract

Neurovascular coupling (NVC) is a fundamental unit that elucidates the regulation of vascular activity by neuronal electrical activity, ensuring adequate blood flow to the brains active regions and optimizing neural function. In this article, we propose a comprehensive dynamic model of a neural vascular coupling network that integrates the capillary K+ sensing mechanism and its impact on vascular motion. Our computational framework incorporates the dynamics of neurons, astrocytes, and smooth muscle cells at the cellular level. By integrating recent experimental findings, we have successfully demonstrated the ability of capillary endothelial cells to detect localized fluctuations in extracellular potassium (K+) concentration via the Kir2.1 channel situated on their membranes. Subsequently, these cells transmit this signal to smooth muscle cells, initiating the release of vasoactive substances and thereby facilitating vascular movement. This sequence of events serves as the fundamental basis of our model. Furthermore, the simulation we provide supports the inclusion of a temperature term in our model, enabling accurate replication of experimental observations: variations in neuronal electrical activity resulting from an increase in temperature and subsequent vasoconstriction. In conclusion, our dynamic model presents a valuable tool for investigating the mechanisms underlying neurovascular coupling and the role of capillary K+ sensing in regulating vascular activity. It enhances our understanding of brain function and offers insights for developing therapeutic interventions for neurovascular diseases. Author summaryIt is widely accepted that neuronal activity induces vasodilation, resulting in increased blood flow, while vascular activity provides energy supply to the nervous system. The role of astrocytes in these processes has been extensively studied, revealing their dual involvement in neuronal firing and facilitation of energy delivery to the nervous system through blood vessels. As cellular mediators of bidirectional processes, astrocytes play a crucial role in promoting neurovascular coupling, leading to the formation of neurovascular coupling units. Building upon existing experimental observations and previous theoretical reports, the present study successfully replicates the phenomenon of vasodilation caused by an increase in potassium ion concentration in the perivascular space, as well as vasoconstriction resulting from elevated potassium ion concentration. A new neuron-astrocyte-endothelial-smooth muscle cell coupling network model, incorporating temperature considerations, was constructed to achieve these outcomes. Additionally, by manipulating temperature, the experimental observation of neuronal vasoconstriction during febrile seizures was successfully reproduced. These results highlight the significance of the neurovascular coupling unit as the fundamental entity for investigating the functions and mechanisms of the nervous system and brain.