Na+, K+, and Cl- transport in resting pancreatic acinar cells

TO understand the role of Na+, K+, and Cl- transporters in fluid and electrolyte secretion by pancreatic acinar cells, we studied the relationship between them in resting and stimulated cells. Measurements of [Cl-](i) in resting cells showed that in HCO3--buffered medium [Cl-](i) and Cl- fluxes are dominated by the Cl-/HCO3- exchanger. In the absence of HCO3-, [Cl-](i) is regulated by NaCl and NaK2Cl cotransport systems. Measurements of [Na+](i) showed that the Na+-coupled Cl- transporters contributed to the regulation of [Na+](i), but the major Na+ influx pathway in resting pancreatic acinar cells is the Na+/H+ exchanger. Rb-86 influx measurements revealed that >95% of K+ influx is mediated by the Nai pump and the NaK2Cl cotransporter. In resting cells, the two transporters appear to be coupled through [K+](i) in that inhibition of either transporter had small effect on Rb-86 uptake, but inhibition of both transporters largely prevented Rb-86 uptake. Another form of coupling occurs between the Na+ influx transporters and the Na+ pump. Thus, inhibition of NaK2Cl cotransport increased Na+ influx by the Na+/H+ exchanger to fuel the Na+ pump. Similarly, inhibition of Na+/H+ exchange increased the activity of the NaK2Cl cotransporter. The combined measurements of [Na+](i) and Rb-86 influx indicate that the Na+/H+ exchanger contributes twice more than the NaK2Cl cotransporter and three times more than the NaCl cotransporter and a tetraethylammonium-sensitive channel to Na+ influx in resting cells. These findings were used to develop a model for the relationship between the transporters in resting pancreatic acinar cells.