NA+ TRANSPORT PATHWAYS IN SECRETORY ACINAR-CELLS - MEMBRANE CROSS-TALK MEDIATED BY [CL-](I)

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 Ca2+-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 Ca2+-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.