Stretch-activated single K+ channels account for whole-cell currents elicited by swelling

Functionally significant stretch-activated ion channels have been clearly i dentified in excitable cells, Although single-channel studies suggest their expression in other cell types, their activity in the whole-cell configura tion has not been shown. This discrepancy makes their physiological signifi cance doubtful and suggests that their mechanical activation is artifactual . Possible roles for these molecules in nonexcitable cells are acute cell-v olume regulation and, in epithelial cells, the complex adjustment of ion fl uxes across individual cell membranes when the rate of transepithelial tran sport changes. We report the results of experiments on isolated epithelial cells expressing in the basolateral membrane stretch-activated K+ channels demonstrable by the cell-attached patch-clamp technique. In these cells, re versible whole-cell currents were elicited by both isosmotic and hyposmotic cell swelling. Cation selectivity and block by inorganic agents were the s ame for single-channel and whole-cell currents, indicating that the same en tity underlies single-channel and whole cell currents and that the single-c hannel events are not artifactual. In these cells, when the rate of apical- membrane NaCl entry increases, the cell Na+ content and volume also increas e, stimulating the Na+,K+-ATPase at the basolateral membrane, i.e., both Na + extrusion and K+ uptake increase, We speculate that, under these conditio ns, the parallel activation of basolateral K+ channels (by the swelling) el evates conductive K+ loss, tending to maintain the cell K+ content constant ("pump-leak parallelism"), This study describes a physiologically relevant stretch-activated channel, at both the single-channel and whole-cell level s, in a nonneural cell type.