A pH-sensitive chloride current in the chemoreceptor cell of rat carotid body

1. Cardiorespiratory response to acidosis is initiated by the carotid body. 2. The direct effect of extracellular pH (pH_o) on the chloride currents of isolated chemoreceptor cells of the rat carotid body was investigated using the whole-cell patch-clamp technique. 3. On applying intra- and extracellular solutions with a symmetrical high-Cl^- content and with the monovalent cations replaced with membrane-impermeant ones, an inwardly rectifying Cl^- current was found. 4. The current activated slowly and did not display any time-dependent inactivation. Current activation was present at membrane potentials negative to 0 mV (pH_o = 7.0). 5. The current was activated by extracellular acidosis and inhibited by alkalosis in the physiologically relevant pH range of 7.0-7.8. 6. The current was reduced by 0.1 mm Cd²⁺ to the level of the leak current and by 1 mM anthracene-9-carboxylic acid (9-AC) to about 40%, while 0.1 mM Ba²⁺ had no effect. 7. Application of 1 mM 9-AC caused a slow but statistically significant increase in the resting pH_i (from a mean of 7.29 to 7.37 in 5 min) in clusters of chemoreceptor cells in CO₂/HCO₃^--buffered media as measured with carboxy-SNARF-1. 8. When membrane potential changes were estimated in the cell-attached mode, 1 mM 9-AC hyperpolarized three out of five tested cells (by 14 mV in average) incubated in CO₂/HCO₃^--buffered media. 9. In summary, chemoreceptor cells express an inwardly rectifying Cl^- current, which is directly regulated by pH_o. The current may participate in intracellular acidification and membrane depolarization during acidic challenge.