Specific expression of salivary maxi-K channel variant is augmented in diabetic mice.

BACKGROUND AND OBJECTIVE: A genetically diabetic mouse strain (db/db) exhibits severe obesity and a syndrome resembling human non-insulin-dependent diabetes mellitus. Our histological study of submandibular glands revealed that the size and area of the granular convoluted tubules was substantially decreased in db/db mice. We hypothesized that this structural difference reflected a specific alteration in salivary duct function. METHODS: The saliva evoked by pilocarpine was used for the measurement of ion concentrations, and submandibular glands were dissected out for the immunohistochemistry and real-time PCR study. RESULTS: The K(+) concentration of the salivary secretion was higher in db/db than in control m+/m+ mice, while neither saliva volume nor the concentrations of Na(+) or Cl⁻ differed between these strains. In db/db mice (vs. m+/m+ mice): quantitative PCR analysis revealed an increased mRNA expression of large-conductance Ca²(+)-activated K(+) (maxi-K) channels, immunohistochemistry revealed an increase in the luminal surface expression of the maxi-K channel protein, and a particularly interesting finding was that there was a substantial increase in the salivary tissue-specific splice variant ParSlo. CONCLUSION: These results suggest that in db/db mice, the K(+) content of saliva may be elevated due to an expression of a maxi-K channel variant, which results from a modification of ductal structure. GENERAL SIGNIFICANCE: Our data may shed some light on the mechanism responsible for determining the dynamics of salivary K(+) concentration increased in diabetic patients.