A model of CO₂ chemotransduction in avian intrapulmonary chemoreceptors

Intrapulmonary chemoreceptors (IPC) are exquisitely sensitive to steady and dynamically changing CO₂ levels in avian lungs, but the mechanism of chemotransduction remains unknown. We sought a model that could explain the following experimental data: (1) hydratable acidic gases like CO₂ and SO₂ inhibit IPC discharge; (2) membrane permeant carbonic anhydrase (CA) inhibitors block CO₂ response and produce near maximal IPC discharge rates (f_IPC) at all CO₂ levels; (3) chronic acclimatization to elevated CO₂ increases f_IPC (and body fluid pH) at any given PCO₂; (4) chronic metabolic acidosis reduces f_IPC (and body fluid pH) at most PCO₂; (5) acute metabolic acidosis or alkalosis (which may not alter intracellular pH_i) has little effect on f_IPC. We propose the following model of IPC chemotransduction: When CO₂ is low, IPC are excited by high pH_i which may directly decrease a repolarizing membrane ton channel conductance (eg. for K⁺), or increase a depolarizing ion channel conductance (eg. for Na⁺). This excitation should rapidly decrease when pH_i falls with elevated PCO₂. We also propose a continuous active transport of H⁺ out of IPC endings with first order kinetics, which gives rise to adaptation with dynamically changing CO₂ signals, and near maximal IPC discharge at all PCO₂ levels when CA is inhibited (pH_i always high). This model may be tested with ion channel blockers and active transport inhibitors.