Major advances in carotid body research: then and now

The carotid body (CB) was anatomically described in the 18th century, and by the early 20th century, it was established as the principal peripheral chemoreceptor that senses arterial blood Po₂, Pco₂, and [H⁺], thereby mediating cardiorespiratory reflex responses. However, the absence of modern electrophysiological and molecular techniques limited the mechanistic insight into stimulus transduction. For decades, the research was dominated by unresolved debates over the mechanisms underlying O₂ and CO₂-H⁺ sensing and the role of putative excitatory transmitters such as dopamine, acetylcholine, and ATP. These uncertainties reflected a major gap between integrative physiology and molecular mechanisms. Since the late 1980s, the situation has changed considerably. Electrophysiological, molecular, and genetic studies have shown that O₂ sensing in glomus cells depends on the coupling between metabolic signals derived from the mitochondrial oxidative metabolism and K⁺ channels activity in the cell membrane. Over the past 20 years, a growing body of evidence has highlighted a novel role for the CB in autonomic-related diseases. An abnormal CB chemosensory overactivity has emerged as an active driver for autonomic dysfunction, featured by sympathetic excitation in conditions such as heart failure, obstructive sleep apnea, severe hypertension, and metabolic alterations. In this review, we will analyze major advances in CB research and the conceptual change from a passive sensor to a key contributor to sympathetic-mediated cardiometabolic diseases.