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Lactate sensing mechanisms in arterial chemoreceptor cells
Hortensia Torres-Torrelo1,2,3, Patricia Ortega-Sáenz1,2,4, Lin Gao1,2,4
1Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
Nature Communications
|July 7, 2021
Summary
Lactate is sensed by the carotid body (CB), not just a metabolic byproduct. CB glomus cells detect lactate, triggering cardiorespiratory reflexes similar to hypoxia.
Area of Science:
- Physiology
- Cellular Biology
- Metabolism
Background:
- Lactate, traditionally seen as an anaerobic metabolism byproduct, is now recognized as a vital fuel source for oxidative phosphorylation and a signaling molecule.
- Elevated blood lactate levels occur in various physiological and pathophysiological states, but the sensing mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of the carotid body (CB) in sensing lactate and maintaining lactate homeostasis.
- To elucidate the cellular mechanisms by which CB glomus cells detect and respond to lactate.
Main Methods:
- Investigated lactate transport into CB glomus cells.
- Measured changes in cytosolic NADH/NAD+ ratio, intracellular pH, and mitochondrial reactive oxygen species (ROS) production.
- Assessed the impact of lactate on glomus cell depolarization, action potential firing, and Ca2+ influx.
Main Results:
- The carotid body (CB) is crucial for lactate homeostasis.
- CB glomus cells function as lactate sensors, responding to lactate via increased NADH/NAD+ ratio, decreased intracellular pH, and enhanced mitochondrial ROS.
- Lactate and hypoxia share downstream signaling pathways to activate glomus cells, potentiating cardiorespiratory reflexes.
Conclusions:
- CB glomus cells are key sensors of blood lactate levels.
- Lactate sensing by the CB contributes to adaptive cardiorespiratory responses.
- This highlights a novel role for lactate as a physiological regulator beyond its metabolic functions.
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