Fig. 2. A model depicting the mechanism of acinar cells fluid and electrolyte secretion.

Shown are the major transporters in the basolateral and luminal membranes of acinar cells and their regulation. The major Cl⁻ loading transporter at the basolateral membrane is NKCC1, with part of the Cl⁻ loading (about 30%) provided by the parallel functioning of NHE1 and AE2. The membrane potential is determined by two Ca²⁺-activated K⁺ channels, the MaxiK and mIK1 channels. TMAM16a/Ano1 is the major Ca²⁺-activated Cl⁻ channel at the luminal membrane that also expresses the water channel AQP5. Fluid and electrolyte secretion by acinar cells is regulated by Ca²⁺-mobilizing receptors and is a Cl⁻ secretion-driven process. The receptor-evoked [Ca²⁺]_i increase initiates at the apical pole where the Ca²⁺ signaling complexes are located to activate TMEM16a/Ano1. The Ca²⁺ signal then propagates to the basal pole to activate the K⁺ channels. The Ca²⁺-mediated channels activation results in luminal Cl⁻ efflux and basolateral K⁺ efflux. Na⁺ then flows through the tight junction to the luminal space. The secretion of NaCl leads to water efflux through AQP5 and cell shrinkage. Cell shrinkage reduces [Ca²⁺]_i to inhibit the Cl⁻ and K⁺ channels and at the same time activates the volume-sensitive NKCC1 (and NHE1 and AE2) to restore cell Cl⁻ and K⁺. The cycle repeats itself during each spike of Ca²⁺ oscillations.