Mercuric chloride alters the membrane potential and intracellular calcium level in mouse pancreatic islet cells

In this study, mercuric chloride was applied to the primary cultures of mouse pancreatic islet cells for studying its effects on resting membrane potential and the intracellular free calcium ion concentration ([Ca 2+), using the techniques of electrophysiology and fluorometry. It was observed that mercuric chloride (1-100 microM) caused a rapid and sustained depolarization, and induced a rapid first phase and a large sustained second phase of elevation in fura-2 fluorescence ratio in islet cells. The depolarization and increased lCa2+]i induced by mercuric chloride could be inhibited by dithiothreitol (a sulfhydryl-containing reducing agent). Removing Ca2+ from the external medium inhibited the mercuric chloride-induced elevation of [Ca2+]i. The increased [Ca2+]i may also originate from the endoplasmic reticulum of pancreatic islet cells, since caffeine (an activator of Ca2+ release from endoplasmic reticulum) and thapsigargin (an inhibitor of endoplasmic reticulum Ca2+-ATPase) could antagonize the effect of mercuric chloride. Moreover, in the absence of glucose in the medium, the response of islet cells to mercuric chloride was a rapid first phase of increased [Ca2+]i followed by a small sustained second phase. Readministration of 5 mM glucose was sufficient but transient to restore sustained phase of increased [Ca2+]i. The increase of [Ca2+]i in islet cells induced by a lower concentration of mercuric chloride (5 microM) was potentiated in higher glucose (7.5 mM) medium. Tolbutamide, an inhibitor of the ATP-sensitive K+-channel, could also inhibit the effect of mercuric chloride. These findings suggest that mercuric chloride initially interacts with the sulfhydryl groups of membrane-bound proteins, which may be an ATP-sensitive K+ channel, to cause depolarization of the islet cells. This depolarization triggers Ca2+ influx and then the release of Ca2+ from the endoplasmic reticulum.