The hypoxic ventilatory response (HVR) is primarily mediated by peripheral chemoreceptors in the carotid body. The oxygen-sensing mechanism in glomus cells involves:

• A Inhibition of mitochondrial complex I by hypoxia → reduced NADH oxidation → decreased cytosolic K⁺ channel conductance → depolarization → Ca²⁺ influx → dopamine/ACh release
• B AMPK activation by low ATP in hypoxia → phosphorylation of KATP channels → closure → depolarization → Ca²⁺ influx → type I cell activation ✓
• C HIF-1α stabilization by hypoxia directly opens TREK-1 K⁺ channels → hyperpolarization → decreased neurotransmitter release
• D Carbon anhydrase-mediated CO₂ sensing in glomus cells secondarily activates pH-sensitive K⁺ channels during hypoxia

Explanation

In carotid body glomus (type I) cells, hypoxia activates AMP-activated protein kinase (AMPK) as cellular ATP falls. AMPK phosphorylates and closes KATP channels (also TASK-1/3 background K⁺ channels are inhibited), causing membrane depolarization. This triggers voltage-gated Ca²⁺ channel opening, Ca²⁺ influx, and exocytosis of dopamine, ATP, and acetylcholine onto sensory nerve endings of the carotid sinus nerve, increasing afferent discharge to the respiratory centres. Central chemoreceptors in the medulla are primarily sensitive to pH/CO₂ and do not mediate the acute HVR. Complex I inhibition and TREK-1 opening are not the primary accepted oxygen-sensing pathways.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.