TASK Channels Regulate Bronchopulmonary C‐Fiber Responsiveness and Reflexes in Guinea Pigs

Chemoreceptors sense changes in systemic O 2 and CO 2 and their dysfunction contributes to serious and life‐threatening diseases. Peripheral chemosensation is attributed primarily to carotid bodies, but bronchopulmonary vagal afferent nerves respond to many of the same stimuli. TWIK‐related acid sensitive potassium (TASK) channels comprised of TASK‐1 and TASK‐3 subunits have been implicated in carotid body chemosensation. Here we show that bronchopulmonary vagal afferent nerves also express TASK channels. The TASK‐1 blocker doxapram (DOX) caused marked and sustained tachypnea and hyperpnea upon iv administration (n=12). CO 2 and lactic acid evoked comparable responses (n=4 each). The tachypnea was abolished by perineural vagal capsaicin desensitization and by midcervical vagotomy (n=3–4). Intra‐arterial DOX evoked only hyperpnea, suggesting a carotid body selective effect (n=5). In vitro , DOX preferentially activated bronchopulmonary C‐fibers arising from the nodose ganglia (n=12). Single‐cell PCR confirmed TASK‐1 and TASK‐3 expression in jugular (n=21) and nodose (n=38) ganglia neurons and revealed that only TRPV‐1 expressing nodose neurons projecting to the airways expressed TASK‐1 in the absence of TASK‐3, which may explain the unique sensitivity of nodose C‐fibers to DOX. These results suggest that TASK‐1 expressing bronchopulmonary C‐fibers play a role in peripheral chemosensation.