title: Na+ transport pathways in secretory acinar cells: membrane cross talk mediated by [Cl-]i.
abstract: Fluid secretion by epithelial cells can be modulated by agents that activate Cl- channels in the apical membrane. To sustain secretion, Cl- influx across the basolateral membrane must also be accelerated. To examine the cellular mechanisms that couple Cl- efflux across the apical membrane to Na(+)-coupled Cl- entry across the basolateral membrane, we employed optical imaging techniques, utilizing single rat salivary acinar cells. Na+ influx was negligible in resting cells but was rapidly increased by carbachol due to activation of a Na(+)-H+ exchanger, a Na(+)-K(+)-2Cl- cotransporter, and, most likely, a nonselective cation channel. Receptor stimulation was not necessary, since elevation of intracellular Ca2+ concentration ([Ca2+]i) by thapsigargin activated the Na+ transporters at equivalent rates. Cell acidification, activation of protein kinase C, cell shrinkage, and other events associated with the rise of [Ca2+]i had little effect on Na+ transport in resting cells. Nevertheless, stimulation of cells in a medium that prevented normal Ca(2+)-induced cell shrinkage prevented activation of all three transport pathways. The block of the activation was not overcome by osmotic shrinkage but was relieved when [Cl-]i was allowed to fall, including conditions in which [Cl-]i fell in the absence of cell shrinkage. Activation of a Na(+)-H+ exchanger, Na(+)-K(+)-2Cl- cotransporter, and nonselective cation channel therefore exhibits a requirement for agonist-induced fall in [Cl-]i. Low [Cl-]i may create a permissive environment for Ca(2+)-dependent activation of multiple Na(+)-transport pathways, providing a mechanism for cross talk that coordinates transport activities of the apical and basolateral membranes in secretory epithelial cells.
authors.affiliation: Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Robertson
authors.forename: J K
authors.initials: JK
authors.lastname: Foskett
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002712:Chlorides; D002217:Carbachol; D012964:Sodium; D011493:Protein Kinase C; D002118:Calcium