Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia

A. Klip, G. B. Mills, B. A.M.E. Britt Elliott

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    Abstract

    The concentration of ionized cytosolic calcium ([Ca2+](i)) was determined in peripheral blood mononuclear cells from normal and malignant hyperthermia (MH)-susceptible humans and pigs, using the fluorescent Ca2+ indicator indo-1. [Ca2+](i) was slightly but significantly elevated in cells from MH human cells relative to normal cells (198 ± 18 nM, n = 15, and 146 ± 14 nM, n = 11, respectively, P < 0.05). Anesthetic concentrations of halothane in the cell suspension resulted in a rapid increase in [Ca2+](i) in cells from both normal and MH humans or pigs. The increases (Δ) were more pronounced in cells from MH subjects than from normal individuals (Δ at 5.7 mM halothane: 245 ± 53 vs. 57 ± 11 nM, respectively) and from MH than from normal pigs (Δ of 241 ± 63 vs. 53 ± 27 nM, respectively). Removal of extracellular Ca2+ obliterated the Δ[Ca2+](i) caused by halothane in cells from normal humans or pigs but only decreased by about half the Δ[Ca2+](i) in cells from MH humans or pigs. In 1,2-bis-(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-loaded cells, in the absence of extracellular Ca2+, halothane failed to increase [Ca2+](i). This suggests that buffering Ca2+(i) with BAPTA precludes detection of release of Ca2+ from intracellular stores, explaining the previous observations made with quin2, a highly chelating Ca2+ indicator. It is concluded that clinical concentrations of halothane allow influx of Ca2+ in cells from both normal and MH-susceptible individuals but release Ca2+ from intracellular stores selectively in cells from the latter group. In cells from MH-susceptible humans and pigs, the anesthetic-induced Δ[Ca2+](i) is higher in the presence of extracellular Ca2+, due in part to concomitant Ca2+ influx from the medium, which directly contributres to the elevation of [Ca2+](i) and may also replenish the intracellular Ca2+ stores.

    Original languageEnglish (US)
    Pages (from-to)C495-C503
    JournalAmerican Journal of Physiology - Cell Physiology
    Volume258
    Issue number3 27-3
    StatePublished - Apr 18 1990

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    Keywords

    • cytosolic calcium
    • general anesthetics
    • indo-1
    • malignant hyperpyrexia

    ASJC Scopus subject areas

    • Physiology
    • Cell Biology

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