Expression of intermediate-conductance, Ca super(2+)-activated K super(+) channel (KCNN4) in H441 human distal airway epithelial cells

• Published in: American journal of physiology. Lung cellular and molecular physiology 2006-11, Vol.291 (5), p.L957-L965
• Main Authors: Wilson, S M, Brown, S G, McTavish, N, McNeill, R P, Husband, E M, Inglis, S K, Olver, R E, Clunes, M T
• Format: Article
• Language: English
• ISSN: 1040-0605

Electrophysiological studies of H441 human distal airway epithelial cells showed that thapsigargin caused a Ca super(2+)-dependent increase in membrane conductance (G sub(Tot)) and hyperpolarization of membrane potential (V sub(m)). These effects reflected a rapid rise in cellular K super(+) conductance (G sub(K)) and a slow fall in amiloride-sensitive Na super(+) conductance (G sub(Na)). The increase in G sub(Tot) was antagonized by Ba super(2+), a nonselective K super(+) channel blocker, and abolished by clotrimazole, a KCNN4 inhibitor, but unaffected by other selective K super(+) channel blockers. Moreover, 1-ethyl-2-benzimidazolinone (1-EBIO), which is known to activate KCNN4, increased G sub(K) with no effect on G sub(Na). RT-PCR-based analyses confirmed expression of mRNA encoding KCNN4 and suggested that two related K super(+) channels (KCNN1 and KCNMA1) were absent. Subsequent studies showed that 1-EBIO stimulates Na super(+) transport in polarized monolayers without affecting intracellular Ca super(2+) concentration ([Ca super(2+)] sub(i)), suggesting that the activity of KCNN4 might influence the rate of Na super(+) absorption by contributing to G sub(K). Transient expression of KCNN4 cloned from H441 cells conferred a Ca super(2+)- and 1-EBIO-sensitive K super(+) conductance on Chinese hamster ovary cells, but this channel was inactive when [Ca super(2+)] sub(i) was