The small conductance K+ channel, KCNQ1 -: Expression, function, and subunit composition in murine trachea

The gene KCNQ1 encodes a K+ channel a-subunit important for cardiac repolarization, formerly known as K,LQT1. In large and small intestine a channel complex consisting of KCNQ1 and the beta -subunit KCNE3 (MiRP2) is known to mediate the cAMP-activated basolateral K+ current, which is essential for luminal Cl- secretion. Northern blot experiments revealed an expression of both subunits in lung tissue. However, previous reports suggested a role of KCNE1 (minK, Isk) but not KCNE3 in airway epithelial cells. Here we give evidence that KCNE1 is not detected in murine tracheal epithelial cells and that Cl- secretion by these cells is not reduced by the knock-out of the KCNE1 gene. In contrast we show that a complex consisting of KCNQ1 and KCNE3 probably forms a basolateral K+ channel in murine tracheal epithelial cells. As described for colonic epithelium, the current through KCNQ1 complexes in murine trachea is specifically inhibited by the chromanol 293B. A 293B-sensitive current was present after stimulation with forskolin and agonists that increase Ca2+ as well as after administration of the pharmacological K+ channel activator, 1-EBIO. A 293B-inhibitable current was already present under control conditions and reduced after administration of amiloride indicating a role of this K+ channel not only for Cl- secretion but also for Na+ reabsorption. We conclude that at least in mice a KCNQ1 channel complex seems to be the dominant basolateral K+ conductance in tracheal epithelial cells.