Carbonic anhydrase activity underlies spike frequency adaptation in avian intrapulmonary chemoreceptors (IPC)

IPC are vagal respiratory afferents that sense intrapulmonary CO 2 and control breathing in birds. Most IPC show spike frequency adaptation (SFA) which helps encode phasic and tonic information about CO 2 changes within each breath. Carbonic anhydrase (CA) is required for CO 2 transduction, and we hypothesized that rapid CA‐catalyzed CO 2 hydration and dehydration underlies SFA in IPC. Small doses of CA inhibitor acetazolamide (AZ) were used to test if phasic IPC CO 2 responses (SFA) could be inhibited independently of tonic CO 2 responses. Single cell IPC spike trains were studied in seven pentobarbital‐anesthetized mallards ( Anas platyrhynchos ). SFA was decreased 23.0% and 66.2% (p<0.05) at 0.5 and 2.0 mg/kg AZ, respectively, while tonic IPC responses were not affected until AZ dosages ≥5 mg/kg. Results suggest that SFA in IPC is due to rapid intracellular CA catalysis of CO 2 hydration resulting in a kinetic overshoot of intracellular pH with abrupt changes in intrapulmonary CO 2 . We present a model of linked differential equations that explores this hypothesis. Support: NIH R15 HL087269–02 and R25 GM056931–15.