The “TASK” of Breathing: Anesthetic Relevance of Background Two-Pore Domain Potassium Channels as Therapeutic Targets for Respiratory Control

Background (leak) potassium (K+) currents, the main contributors to resting membrane potential in excitable cells, are mediated by channels of the 2-pore domain (K2P) family. In the respiratory system, the TWIK-related acid-sensitive K+ channel (TASK) subfamily is proposed to mediate key functions in the carotid body type I glomus cells, central chemoreceptors and respiratory center, pulmonary arteries, and upper airway musculature. K2P channels are also located throughout the central nervous system, notably in the hypoglossal motor neurone pool, regions involved in sleep-wake regulation and pain perception. Being sensitive to general anesthetics, K2P channels may mediate both the adverse respiratory effects and hypnotic actions of many anesthetics. Therefore, they offer potential as pharmacological targets to reverse postoperative respiratory depression, ameliorate anesthetic risks of obstructive sleep apnea, improve ventilation-perfusion matching, and even assist in the active recovery from hypnotic effects of anesthesia during emergence from surgery.