Na⁺ entry via store-operated Ca²⁺ channels in mouse submandibular acinar cells.

Abstract

We reported previously that two store-operated Ca²⁺ channels (SOCs) could be separated by using Zn²⁺ in the submadibular acinar cells. In short, after depleting the Ca²⁺ stores with thapsigargin, SOC signals during readmission of external Ca²⁺ were detected. The signal showed two phases; the initial large transient and subsequent sustained phase. External Zn²⁺ inhibited the former but not the latter. External Ni²⁺ or excess of outside K⁺ markedly reduced both. Based on this observation, we studied Na⁺ entry through SOC. Loading benzofrane isophthalate (SBFI)-AM for 2 h at 37^oC to the cells, internal [Na⁺]_i was monitored with digital imaging methods. Prior elimination of external Na⁺ (replaced with an impermeable cation, NMDG⁺) induced a substantial increase in Na⁺ entry by Na⁺ readmission, and it was strengthened by a simultaneous elimination of external Ca²⁺. When Ca²⁺ stores were actively depleted with thapsigargin under Ca²⁺- and Na⁺-free condition, the largest Na⁺ signals were counted by the Na⁺ readmission. In contrast to the pattern of Ca²⁺ entry, that of Na⁺ was monophasic and inhibited by external Zn²⁺, Ni²⁺ and Ca²⁺ as well. The finding that external Ca²⁺ reduced Na⁺ signals suggests that Ca²⁺ store depletion induces Na⁺ entry through SOCs in a competitive manner with Ca²⁺. Collectively, after depletion of Ca²⁺ stores, Na⁺ may enter into the cells through the divalent cation-sensitive Ca²⁺-entry pathway in mouse submandibular acinar cells. [J Physiol Sci. 2006;56 Suppl:S109]