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1Centre de recherche, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Québec H2W 1T7; and 2Département de médecine, Université de Montréal, Montréal, Québec H3C 3J7, Canada
Submitted 24 July 2003 ; accepted in final form 4 January 2004
K+ channels play a crucial role in epithelia by repolarizing cells and maintaining electrochemical gradient for Na+ absorption and Cl- secretion. In the airway epithelium, the most frequently studied K+ channels are KvLQT1 and KCa. A functional role for KATP channels has been also suggested in the lung, where KATP channel openers activate alveolar clearance and attenuate ischemia-reperfusion injury. However, the molecular identity of this channel is unknown in airway and alveolar epithelial cells (AEC). We adopted an RT-PCR strategy to identify, in AEC, cDNA transcripts for Kir channels (Kir6.1 or 6.2) and sulfonylurea receptors (SUR1, 2A, or 2B) forming KATP channels. Only Kir6.1 and SUR2B were detected in freshly isolated and cultured alveolar cells. To determine the physiological role of K+ channels in the transepithelial transport of alveolar monolayers, we studied the effect, on total short-circuit currents (Isc), of basolateral application of glibenclamide, an inhibitor of KATP channels, as well as clofilium, charybdotoxin, clotrimazole, and iberiotoxin, inhibitors of KvLQT1 and KCa channels, respectively. Interestingly, activity of the three types of K+ channels was detected, since all tested inhibitors decreased Isc. Furthermore, these K+ channel inhibitors reduced amiloride-sensitive Na+ currents (mediated by ENaC) and completely abolished stimulation of Cl- currents by forskolin. Conversely, pinacidil, an activator of KATP channels, increased Na+ and Cl- transepithelial transport by 33–35%. These results suggest the presence, in AEC, of a KATP channel, formed from Kir6.1 and SUR2B subunits, which plays a physiological role, with KvLQT1 and KCa channels, in Na+ and Cl- transepithelial transport.
lung; ATP-sensitive K+ channel; Kir6.1/SUR2B; Na+ and Cl- transepithelial transport
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