A 50-year-old man with COPD has a PaO2 of 52 mmHg. His peripheral chemoreceptors (carotid bodies) detect this hypoxemia. Which ion channel mechanism in glomus cells initiates the chemoreceptor response?
- A H+-gated Na+ channels (ASIC channels) activated by local acidosis from hypoxic metabolism
- B Hypoxia-sensitive KATP channels open in glomus cells → K+ efflux → hyperpolarization → inhibitory response
- C O2-sensitive background K+ channels (TASK-1/TASK-3, TREK) are inhibited by hypoxia → membrane depolarization → voltage-gated Ca2+ entry → neurotransmitter release (dopamine, ACh) ✓
- D HIF-1α directly opens cyclic nucleotide-gated channels causing immediate depolarization in glomus cells
Explanation
Carotid body glomus (type I) cells sense O2 via mitochondrial heme proteins that inhibit O2-sensitive two-pore-domain K+ channels (TASK-1, TASK-3, and TREK-1/TREK-2) during hypoxia. Inhibition of these background K+ leak channels reduces K+ efflux, causing membrane depolarization. This opens voltage-gated L-type Ca2+ channels → Ca2+ influx → exocytosis of neurotransmitters (dopamine, ATP, substance P, ACh) → activates afferent sinus nerve (IX) → NTS → increased respiratory drive. KATP channel opening would cause hyperpolarization (opposite effect). HIF-1α is a transcription factor for long-term adaptation, not immediate signaling.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.