Extracellular Mg2+Inhibits both Histamine-Stimulated Ca2+-Signaling and Exocytosis in Human Tracheal Secretory Gland Cells

Abstract

The effects of extracellular Mg2+concentration have been investigated on the histamine-stimulated exocytotic process of human tracheal secretory gland (HTG) cells. The exocytosis of secretory granules (SG) was observed concomitantly with dynamic changes of intracellular Ca2+([Ca2+]i) and Mg2+concentrations ([Mg2+]i). The rate of SG exocytosis was appraised by the decrease of quinacrine fluorescence emission. Dynamic changes of [Mg2+]iand [Ca2+]iin HTG cells were determined by the combined use of UV-microspectrofluorometry with Mag-Indo-1 and Indo-1 probes, respectively. High Mg2+medium significantly inhibited the histamine-stimulated secretion. The influence of the extracellular and intracellular Mg2+concentrations on [Ca2+]iwas analyzed. Basal [Mg2+]iincreased from 0.8 mM in a Mg2+-free medium to 1.7 mM in 10 mM Mg2+medium. Histamine induced a [Mg2+]iincrease which is dependent on extracellular Mg2+concentration. The histamine stimulated [Ca2+]irise was reduced in the presence of elevated Mg2+extracellular medium and inhibitory effects of extracellular Mg2+were concomitant with changes in [Mg2+]i. Our data suggest that the inhibition by extracellular Mg2+of stimulated exocytosis is dependent on both the increase of [Mg2+]iand the inhibition of cytosolic Ca2+influx.