Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the <i>Clcn3</i> Cl<sup>−</sup> channel gene

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<jats:p>Salivary gland acinar cells shrink when Cl<jats:sup>−</jats:sup> currents are activated following cell swelling induced by exposure to a hypotonic solution or in response to calcium‐mobilizing agonists. The molecular identity of the Cl<jats:sup>−</jats:sup> channel(s) in salivary cells involved in these processes is unknown, although ClC‐3 has been implicated in several tissues as a cell‐volume‐sensitive Cl<jats:sup>−</jats:sup> channel. We found that cells isolated from mice with targeted disruption of the <jats:italic>Clcn3</jats:italic> gene undergo regulatory volume decrease in a fashion similar to cells from wild‐type littermates. Consistent with a normal regulatory volume decrease response, the magnitude and the kinetics of the swell‐activated Cl<jats:sup>−</jats:sup> currents in cells from ClC‐3‐deficient mice were equivalent to those from wild‐type mice. It has also been suggested that ClC‐3 is activated by Ca<jats:sup>2+</jats:sup>‐calmodulin‐dependent protein kinase II; however, the magnitude of the Ca<jats:sup>2+</jats:sup>‐dependent Cl<jats:sup>−</jats:sup> current was unchanged in the <jats:italic>Clcn3</jats:italic><jats:sup>−/‐</jats:sup> animals. In addition, we observed that ClC‐3 appeared to be highly expressed in the smooth muscle cells of glandular blood vessels, suggesting a potential role for this channel in saliva production by regulating blood flow, yet the volume and ionic compositions of <jats:italic>in vivo</jats:italic> stimulated saliva from wild‐type and null mutant animals were comparable. Finally, in some cells ClC‐3 is an intracellular channel that is thought to be involved in vesicular acidification and secretion. Nevertheless, the protein content of saliva was unchanged in <jats:italic>Clcn3</jats:italic><jats:sup>−/‐</jats:sup> mice. Our results demonstrate that the ClC‐3 Cl<jats:sup>−</jats:sup> channel is not a major regulator of acinar cell volume, nor is it essential for determining the secretion rate and composition of saliva.</jats:p>

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