TASK, a human background K+ channel to sense external pH variations near physiological pH

Abstract

TASK is a new member of the recently recognized TWIK K+ channel family. This 395 amino acid polypeptide has four transmembrane segments and two P domains. In adult human, TASK transcripts are found in pancreas<placenta<brain<lung, prostate<heart, kidney<uterus, small intestine and colon. Electrophysiological properties of TASK were determined after expression in Xenopus oocytes and COS cells. TASK currents are K+-selective, instantaneous and non-inactivating. They show an outward rectification when external [K+] is low ([K+]out = 2 mM) which is not observed for high [K+]out (98 mM). The rectification can be approximated by the Goldman-Hodgkin-Katz current equation that predicts a curvature of the current-voltage plot in asymmetric K+ conditions. This strongly suggests that TASK lacks intrinsic voltage sensitivity. The absence of activation and inactivation kinetics as well as voltage independence are characteristic of conductances referred to as leak or background conductances. For this reason, TASK is designated as a background K+ channel. TASK is very sensitive to variations of extracellular pH in a narrow physiological range; as much as 90% of the maximum current is recorded at pH 7.7 and only 10% at pH 6.7. This property is probably essential for its physiological function, and suggests that small pH variations may serve a communication role in the nervous system.