Figure 7. Flow-stimulated Na⁺ currents are regulated by extracellular ATP.

Whole-cell currents were measured during basal conditions and during exposure to flow (shear =0.24 dyne/cm²) in the absence or presence of ATP (100 μM) or apyrase (5 unit/ml). A. Representative whole-cell recording with currents measured at −100 mV and at 100 mV shown. Flow exposure (shear of 0. 24 dyne/cm²) is indicated by the top bar. Currents activated rapidly with the onset of flow and were partially inhibited when ATP was included in the perfusate as indicated by the lower line. Subsequent removal of ATP and addition of apyrase resulted in rapid activation of currents. Re-application of ATP inhibited currents. B. Cumulative data demonstrating maximal flow-stimulated current density in control conditions or in the presence of ATP, or apyrase. Values represent maximal current density measured at −100 mV (n=4-5 each), *p< 0.05 versus control, **p<0.01 versus control. C. Proposed model for the coordination of biliary epithelial secretion and absorption by extracellular ATP. According to this model, when the concentration of ATP in bile is high, TMEM16A is activated, ENaC is inhibited, and net secretion occurs. When the concentration of ATP in bile drops, TMEM16A inactivates, the inhibitory effect of ATP on ENaC is abolished, and net absorption occurs.