The reasoning: a distributed closed loop
- Rhythm: the preBötzinger complex (ventrolateral medulla) generates inspiratory rhythm; the ventral respiratory column (rostral and caudal VRG premotor neurons), dorsal respiratory group (NTS — afferent integration), parafacial/RTN (active expiration, CO₂ sensing) and pontine Kölliker–Fuse/parabrachial nuclei (phase switching — historical "pneumotaxic centre") shape the pattern. Output: phrenic (C3–C5), intercostal, upper‑airway and abdominal motor neurons.
- Central chemoreceptors (RTN and distributed neurons/glia near the ventral medullary surface) sense brain interstitial H⁺ derived from CO₂ — CO₂ crosses the BBB freely; H⁺ and HCO₃⁻ do not. They provide ~⅔ of the steady‑state CO₂ response. CSF HCO₃⁻ adjusts over days (chronic hypercapnia, altitude), resetting sensitivity.
- Peripheral chemoreceptors (carotid bodies → CN IX; aortic bodies → CN X) sense PaO₂ (not content), plus PaCO₂ and H⁺, within seconds. Glomus (type I) cells: hypoxia inhibits O₂‑sensitive K⁺ channels → depolarisation → Ca²⁺ entry → transmitter release (ATP, ACh, dopamine). They are the only source of the hypoxic ventilatory response and mediate the rapid response to metabolic acidosis.