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A Ba²⁺-resistant, acid-sensitive K⁺ conductance in Na⁺-absorbing H441 human airway epithelial cells

Lung Membrane Transport Group, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland

Submitted 27 October 2006 ; accepted in final form 26 January 2007

By analysis of whole cell membrane currents in Na⁺-absorbing H441 human airway epithelial cells, we have identified a K⁺ conductance (G_K) resistant to Ba²⁺ but sensitive to bupivacaine or extracellular acidification. In polarized H441 monolayers, we have demonstrated that bupivacaine, lidocaine, and quinidine inhibit basolateral membrane K⁺ current (I_Bl) whereas Ba²⁺ has only a weak inhibitory effect. I_Bl was also inhibited by basolateral acidification, and, although subsequent addition of bupivacaine caused a further fall in I_Bl, acidification had no effect after bupivacaine, demonstrating that cells grown under these conditions express at least two different bupivacaine-sensitive K⁺ channels, only one of which is acid sensitive. Basolateral acidification also inhibited short-circuit current (I_SC), and basolateral bupivacaine, lidocaine, quinidine, and Ba²⁺ inhibited I_SC at concentrations similar to those needed to inhibit I_Bl, suggesting that the K⁺ channels underlying I_Bl are part of the absorptive mechanism. Analyses using RT-PCR showed that mRNA encoding several two-pore domain K⁺ (K2P) channels was detected in cells grown under standard conditions (TWIK-1, TREK-1, TASK-2, TWIK-2, KCNK-7, TASK-3, TREK-2, THIK-1, and TALK-2). We therefore suggest that K2P channels underlie G_K in unstimulated cells and so maintain the driving force for Na⁺ absorption. Since this ion transport process is vital to lung function, K2P channels thus play an important but previously undocumented role in pulmonary physiology.

airway sodium channel transport; patch clamping; Ussing chamber

This article has been cited by other articles:

				S. G. Brown, M. Gallacher, R. E. Olver, and S. M. Wilson The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L942 - L954. [Abstract] [Full Text] [PDF]