title: Mercuric chloride alters the membrane potential and intracellular calcium level in mouse pancreatic islet cells.
abstract: 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.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei. shliu@ha.mc.ntu.edu.tw
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.forename: Shoei-Yn
authors.initials: SY
authors.lastname: Lin-Shiau
mesh_terms: D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D018929:Cell Culture Techniques; D004202:Disinfectants / Q000009:adverse effects*; D004594:Electrophysiology; D005470:Fluorometry; D007424:Intracellular Fluid / Q000737:chemistry; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects*; D008627:Mercuric Chloride / Q000009:adverse effects*; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D004202:Disinfectants; D008627:Mercuric Chloride; D002118:Calcium