Molecular mechanisms of secretory responses in nasal gland acinar cells

Abstract

We clarified regulatory signal transduction mechanisms of the acinar cells of the mammalian nasal gland using patch-clam techniques and fluorescence ratio imaging microscopy. Acetylcholine (ACh) indirectly activates both Cl⁻ and K⁺ channels by raising intracellular Ca²⁺. Subsequent membrane depolarization resulting from Cl⁻ efflux via the Cl⁻ channels in the luminal membrane leads to further activation of the basolateral K⁺ channels and a favorable electrochemical gradient for K⁺ efflux. Both K⁺ and CI⁻ enter the cell mediated by Na⁺-K⁺ATPase and Na-K-CI cotransport. The Na-K-CI cotransport is activated directly by increased Ca²⁺ presumably involving phosphorylation by Ca²⁺/Calmodulin-dependent myosin light chain kinase. The resultant luminal negativity draws Na’ into the lumen via the paracellular pathway. The activation of the Cl⁻ channel plays a critical role in producing isotonic glandular secretion rich in NaCl. Several medicines affect stimulus-response coupling mediated by the above-mentioned cellular signaling pathways.