Simulation of Conducted Responses in Microvascular Networks: Role of Gap Junction Current Rectification

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2025-02-13 DOI:10.1111/micc.70002

Sara Djurich, Grace V. Lee, Timothy W. Secomb

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引用次数: 0

Abstract

Objective

Local control of blood flow depends on signaling to arterioles via upstream conducted responses. Here, the objective is to examine how electrical properties of gap junctions between endothelial cells (EC) affect the spread of conducted responses in microvascular networks of the brain cortex, using a theoretical model based on EC electrophysiology.

Methods

Modeled EC currents are an inward-rectifying potassium current, a non-voltage-dependent potassium current, a leak current, and a gap junction current between adjacent ECs. Effects of varying gap junction conductance are considered, including asymmetric conductance, with higher conductance for forward currents (positive currents from upstream to downstream, based on blood flow direction). The response is initiated by a local increase in extracellular potassium concentration. The model is applied to a 45-segment synthetic network and a 4881-segment network from mouse brain cortex.

Results

The conducted response propagates preferentially to upstream arterioles when the conductance for forward currents is at least 20 times that for backward currents. The response depends strongly on the site of stimulation. With symmetric gap junction conductance, the network acts as a syncytium and the conducted response is dissipated.

Conclusions

Upstream propagation of conducted responses may depend on the asymmetric conductance of EC gap junctions.

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微血管网络传导响应的模拟：缝隙结电流整流的作用

目的局部血流控制依赖于通过上游传导反应向小动脉传递信号。本研究的目的是利用基于内皮细胞电生理学的理论模型，研究内皮细胞间隙连接的电特性如何影响大脑皮层微血管网络传导反应的传播。模拟的EC电流包括一个向内整流的钾电流、一个非电压依赖的钾电流、一个漏电流和一个相邻EC之间的间隙结电流。考虑了不同间隙结电导的影响，包括不对称电导，正向电流（基于血流方向从上游到下游的正电流）具有更高的电导。这种反应是由细胞外钾浓度的局部增加引起的。该模型应用于小鼠大脑皮层的45段合成网络和4881段网络。结果当正向电流的电导至少为反向电流的20倍时，传导响应优先向上游小动脉传播。这种反应很大程度上取决于刺激的部位。在对称间隙结电导率下，网络充当合胞体，传导响应被耗散。结论传导响应的上游传播可能取决于EC间隙连接的不对称电导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.