Capillary-arteriolar communication in oxygen demand-supply coupling in skeletal muscle

What is it about?

Matching oxygen supply to tissue demand is a vital process achieved by fine adjustments in microvascular red blood cell flow. How these responses are triggered and communicated in microvascular networks of skeletal muscle is currently debated. A potential mechanism involves activation of potassium-sensitive channels by extracellular potassium, leading to arterial hyperpolarization and vasodilation. Using a customized experimental setup, we show that capillary communication with arterioles occurs via signals that spread through gap junctions composed of Cx40 (connexin40) to match red blood cell flow to oxygen needs in skeletal muscle; these responses are not triggered by hypoxia or extracellular potassium.

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Photo by Solen Feyissa on Unsplash

Photo by Solen Feyissa on Unsplash

Why is it important?

Our study shows that capillaries are the site where oxygen requirements are sensed and blood flow responses are initiated, which entails communication between capillaries and upstream arterioles. This work challenges the idea that hypoxia triggers microcirculatory responses in healthy muscle and is also inconsistent with the idea of extracellular potassium as the mediator. These findings refocus the oxygen demand–supply coupling paradigm in skeletal muscle to oxygen as the stimulus, microcirculation as the sensor, and capillaries as the site of initiation of conducted hyperpolarization, ultimately leading to arteriolar vasodilation and increased blood flow.

Perspectives