KATP channel-dependent electrical signaling links capillary pericytes to arterioles during neurovascular coupling

• 成果类型: Article
• 署名作者: Isaacs, Dominic; Xiang, Liuruimin; Hariharan, Ashwini; Longden, Thomas A.
• 署名单位: University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11305
• DOI: 10.1073/pnas.2405965121
• 发表日期: 2024-12-10
• 关键词: cerebral-blood-flow; smooth-muscle; brain; stimulation; HEALTH

摘要

The brain has evolved mechanisms to dynamically modify blood flow, enabling the timely delivery of energy substrates in response to local metabolic demands. Several such neurovascular coupling (NYC) mechanisms have been identified, but the vascular signal transduction and transmission mechanisms that enable dilation of penetrating arterioles (PAs) remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of NYC. Recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the diameter of upstream vessels. Thin- strand pericyte cell bodies and processes cover around 90% of the capillary bed, and here we show that these cells play a central role in sensing neural activity and generating and relaying electrical signals to arterioles. We identify a K ATP channel-dependent neurovascular signaling pathway that is explained by the recruitment of thin- strand pericytes and we deploy vascular optogenetics to show that currents generated in individual thin- strand pericytes are sent over long distances to upstream arterioles to cause dilations in vivo. Genetic disruption of vascular K ATP channels reduces the arteriole diameter response to neural activity and laser ablation of thin- strand pericytes eliminates the K ATP- dependent component of NYC. Together, our findings indicate that thin- strand pericytes sense neural activity and transform this into K ATP channel-dependent electrometabolic signals that inform upstream arterioles of local energy needs, promoting spatiotemporally precise energy distribution.