Regulation of cough by neuronal Na+–K+ ATPases

•Na+–K+ ATPases play an essential role in regulating the excitability of the vagal afferent nerves encoding the cough reflex.•Sodium pump inhibitors prevent coughing in animal models and in patients.•Isozyme selective inhibitors of the sodium pumps may provide cough relief without side effects.

The Na+–K+ ATPases play an essential role in establishing the sodium gradients in excitable cells. Multiple isoforms of the sodium pumps have been identified, with tissue and cell specific expression patterns. Because the vagal afferent nerves regulating cough must be activated at sustained high frequencies of action potential patterning to achieve cough initiation thresholds, it is a certainty that sodium pump function is essential to maintaining cough reflex sensitivities in health and in disease. The mechanisms by which Na+–K+ ATPases regulate bronchopulmonary vagal afferent nerve excitability are reviewed as are potential therapeutic strategies targeting the sodium pumps in cough.