CO2 transduction in avian intrapulmonary chemoreceptors is critically dependent on transmembrane Na+/H+ exchange

Avian intrapulmonary chemoreceptors (IPC) are vagal respiratory afferents that are inhibited by high lung Pco 2 and excited by low lung Pco 2. Previous work suggests that increased CO2 inhibits IPC by acidifying intracellular pH (pHi) and that pHi is determined by a kinetic balance between the rate of intracellular carbonic anhydrase-catalyzed CO2 hydration/dehydration and transmembrane extrusion of acids and/or bases by various exchangers. Here, the role of amiloride-sensitive Na+/H+ exchange (NHE) in the IPC CO2 response was tested by recording single-unit action potentials from IPC in anesthetized ducks, Anas platyrhynchos. For each of the IPC tested, blockade of the NHE using dimethyl amiloride (DMA) elicited a marked (>50%) dose-dependent decrease in mean IPC discharge (P < 0.05), suggesting that NHE is important for pHi regulation and CO2 transduction in IPC. In addition, activation of the NHE using 12-O-tetradecanoylphorbol 13-acetate stimulated six of the seven IPC tested, although the overall eff...