The Small Conductance K+ Channel, KCNQ1

Abstract

The gene KCNQ1 encodes a K ؉ channel ␣-subunit important for cardiac repolarization, formerly known as K v LQT1. In large and small intestine a channel complex consisting of KCNQ1 and the ␤-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 Ca 2؉ 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.

KCNE1 and KCNE3: The yin and yang of voltage-gated K+ channel regulation

“…The cell-specific expression, biological functions and α subunit partners of KCNE1 in the kidneys remain a matter of debate 112–116 . KCNE1 was also previously suggested to form channels with KCNQ1 in the airway epithelium, but it now appears much more likely that KCNQ1-KCNE3 complexes are expressed there instead (see below) 117 .…”

“…As observed for the intestine, Kcne3 deletion in mice also disrupts tracheal Cl − secretion, and basolateral KCNQ1-KCNE3 complexes are thought to be required for cAMP-stimulated Cl − secretion in the airway epithelium. KCNQ1-KCNE3 channels may also facilitate Na + reabsorption in the airways of mice 117 . Again, data for the potential role of KCNQ1-KCNE3 in human airway epithelia are currently lacking.…”

KCNQ1-dependent transport in renal and gastrointestinal epithelia

“…For analysis of electrogenic intestinal amino acid and glucose transport, proximal jejunal segments (5-10 cm after the pylorus) were mounted into a custom-made miniUssing chamber (22). Under control conditions, the serosal and luminal perfusate contained the following: 100 mM NaCl, 2 mM KCl, 1 mM MgCl 2 , 1.25 mM CaCl 2 , 0.4 mM KH 2 PO 4 , 1.6 mM K 2 HPO 4 , 5 mM sodium pyruvate, 25 mM NaHCO 3 , 20 mM mannitol (pH 7.4), and 1 M indomethacin (Sigma) to prevent prostaglandin E 2 -stimulated Cl Ϫ secretion.…”

Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice

“…The addition of forskolin/IBMX induced a negative shift in V te and increased the lumen negative I sc . It is well known that luminal Cl - channels (CFTR) and basolateral K + channels (KCNQ1) are activated by cAMP-dependent signalling pathways (17, 18). Consistent with this model, the application of the KCNQ1 channel blocker (100 µM of chromanol 293B) to the basolateral side suppressed the cAMP-induced I sc .…”