UNASSIGNED: The renal epithelial @entity1372 channel ( @entity28919 ) provides regulated @entity1372 transport in the distal nephron. The effects of intracellular @entity460 ([ @entity141 ]i) on this channel are only beginning to be elucidated. It appears from previous studies that the [ @entity141 ]i increases downstream of @entity855 administration may have a polarized effect on @entity28919 where apical application of @entity855 and subsequent [ @entity141 ]i increase has an inhibitory effect on the channel whereas basolateral @entity855 and [ @entity141 ]i have a stimulatory effect. We asked if this polarized effect of @entity855 is in fact reflective of a polarized effect of increased [ @entity141 ]i on @entity28919 and what underlying mechanism is responsible. We began by performing patch clamp experiments in which @entity28919 activity was measured during apical or basolateral application of @entity1360 to increase [ @entity141 ]i near the apical or basolateral membrane, respectively. We found that @entity28919 does indeed respond to increased [ @entity141 ]i in a polarized fashion, with apical increases being inhibitory and basolateral stimulating channel activity. In other epithelial cell types, mitochondria sequester [ @entity141 ]i, creating [ @entity141 ]i signaling microdomains within the cell that are dependent on mitochondrial localization. We found that mitochondria localize in bands just beneath the apical and basolateral membranes in two different cortical collecting duct principal cell lines and in cortical collecting duct principal cells in @entity19 kidney tissue. We found that inhibiting mitochondrial [ @entity141 ]i uptake destroyed the polarized response of @entity28919 to [ @entity141 ]i. Overall, our data suggest that @entity28919 is regulated by [ @entity141 ]i in a polarized fashion and that this polarization is maintained by mitochondrial [ @entity141 ]i sequestration.

Polarized Effect of Intracellular @entity460 on the Renal Epithelial XXXX Channel Occurs as a Result of Subcellular @entity460 Signaling Domains Maintained by Mitochondria.

@entity19 :: ('10090', 'Species') :: ['mouse'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity28919 :: ('20276(Tax:10090)', 'Gene') :: ['ENaC'] @entity1360 :: ('MESH:D015759', 'Chemical') :: ['ionomycin'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity1372 :: (MESH:D012964,Chemical) :: ['Sodium']
