https://doi.org/10.1152/ajpcell.00672.2024

Pulmonary ionocytes express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) channels. When studied using the short-circuit current technique, ionocytes produce CFTR-dependent short-circuit currents consistent with Cl⁻ secretion. However, when studied without a voltage clamp, data indicate that ionocytes absorb Cl⁻. In this review, we resolve these seemingly conflicting findings by considering the different transepithelial voltages and the resultant movement of Cl⁻ during short circuit and physiological open-circuit conditions. This analysis indicates that behavior under short-circuit conditions cannot be directly extrapolated to infer behavior under physiologic conditions. Finally, we discuss the potential role of basolateral Cl⁻ channels in controlling absorption and secretion in ionocytes.