Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans-Partial revision of our current knowledge required.

Appropriate composition of oral saliva is essential for a healthy milieu that protects mucosa and teeth. Only few studies, with small sample numbers, investigated physiological saliva ion composition in humans. We determined saliva ion composition in a sufficiently large cohort of healthy adults and analyzed the effect of physiological stimulation. We collected saliva from 102 adults under non-stimulated and physiologically stimulated conditions (chewing). Individual flow rates, pH, osmolality, Na, K, Cl, and HCO concentrations under both conditions as well as the individual changes due to stimulation (Δvalues) were determined. Non-stimulated saliva was hypoosmolal and acidic. Na, Cl, and HCO concentrations remained well below physiological plasma values, whereas K concentrations exceeded plasma values more than twofold. Stimulation resulted in a doubling of flow rates and substantial increases in pH, HCO, and Na concentrations. Overall, stimulation did not considerably affect osmolality nor K or Cl concentrations of saliva. An in-depth analysis of stimulation effects, using individual Δvalues, showed no correlation of Δflow rate with Δion concentrations, indicating independent regulation of acinar volume and ductal ion transport. Stimulation-induced Δ[Na] correlated with Δ[HCO] and Δ[Cl] but not with Δ[K], indicating common regulation of ductal Na, Cl, and HCO transport. We present a robust data set of human oral saliva ion composition in healthy adults and functional insights into physiological stimulation. Our data show (i) that flow-dependence exists for Na and HCO but not for K and Cl concentrations, (ii) osmolality is flow-independent, (iii) regulation of Na, Cl, and HCO transport is coupled, (iv) regulation of flow rate and ion concentrations are independent and (v) spatially separated between acini and ducts, respectively.