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Thiol oxidation by ...
Thiol oxidation by 2,2'-dithiodipyridine causes a reversible increase in cytoplasmic free Ca2+ concentration in pancreatic beta-cells : Role for inositol 1,4,5-trisphosphate-sensitive Ca2+ stores
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- Islam, M. Shahidul (author)
- Karolinska Institutet,Uppsala universitet,Medicin
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Kindmark, Henrik (author)
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Larsson, Olof (author)
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- Berggren, Per-Olof (author)
- Karolinska Institutet
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(creator_code:org_t)
- Portland Press Ltd. 1997
- 1997
- English.
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In: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 321:Pt 2, s. 347-354
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Abstract
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- 2,2'-Dithiodipyridine (2,2'-DTDP), a reactive disulphide that mobilizes Ca2+ from ryanodine-sensitive Ca2+ stores in muscle, induced a biphasic increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells loaded with fura 2. This increase consisted of an early transient followed by a second, slower, rise. The [Ca2+]i transient was dependent on extracellular Ca2+ and disappeared on treatment with nimodipine. The reactive disulphide caused plasma membrane depolarization, as studied by the perforated-patch configuration of the patch-clamp technique. Hence membrane depolarization and opening of the L-type voltage-gated Ca2+ channels were responsible for the first transient in [Ca2+]i. The second slower increase in [Ca2+]i was prolonged but readily reversed by the disulphide-reducing agent 1,4-dithiothreitol. This increase in [Ca2+]i was not decreased by nimodipine or by omission of extracellular Ca2+, but was eliminated when the Ins(1,4,5)P3-sensitive Ca2+ pool was first depleted by carbachol. Ryanodine or its beta-alanyl analogue did not release Ca2+ from intracellular stores, and a high concentration of ryanodine did not inhibit Ca2+ release by 2,2'-DTDP. The disulphide compound suppressed glucose metabolism and decreased the mitochondrial inner-membrane potential. We conclude that thiol oxidation by 2,2'-DTDP affects Ca2+ homeostasis in beta-cells by multiple mechanisms. However, unlike the situation in muscle, in beta-cells 2,2'-DTDP releases Ca2+ from intracellular pools by mechanisms that do not involve activation of ryanodine receptors. Instead, in these cells the Ins(1,4,5)P3-sensitive intracellular Ca2+ store comprises an alternative target for the Ca(2+)-mobilizing action of the reactive disulphide compound.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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