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

Fluid secretion by epithelial cells can be modulated by agents that ac tivate Cl- channels in the apical membrane. To sustain secretion, Cl- influx across the basolateral membrane must also be accelerated. To ex amine 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 ac inar 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 chan nel. Receptor stimulation was not necessary, since elevation of intrac ellular Ca2+ concentration ([Ca2+](i)) by thapsigargin activated the N a+ transporters at equivalent rates. Cell acidification, activation of protein kinase C, cell shrinkage, and other events associated with th e rise of [Ca2+](i) had little effect on Na+ transport in resting cell s. Nevertheless, stimulation of cells in a medium that prevented norma l Ca2+-induced cell shrinkage prevented activation of all three transp ort pathways. The block of the activation was not overcome by osmotic shrinkage but was relieved when [Cl-](i) was allowed to fall, includin g conditions in which [Cl-](i) fell in the absence of cell shrinkage. Activation of a Na+-H+ exchanger, Na+-K+-2Cl(-) cotransporter, and non selective cation channel therefore exhibits a requirement for agonist- induced fall in [Cl-](i). Low [Cl-](i) may create a permissive environ ment for Ca2+-dependent activation of multiple Na+-transport pathways, providing a mechanism for cross talk that coordinates transport activ ities of the apical and basolateral membranes in secretory epithelial cells.