Premium
Synergistic action of calcium‐lonophores and hyperthermia is best interpreted as thermal enhancement of calcium toxicity
Author(s) -
Stege G. J. J.,
Wierenga P. K.,
Konings A. W. T.,
Kampinga H. H.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041550304
Subject(s) - ionomycin , calcium , extracellular , toxicity , ionophore , hyperthermia , intracellular , calcium in biology , biophysics , chemistry , cell culture , pharmacology , biochemistry , microbiology and biotechnology , biology , medicine , genetics , organic chemistry
It has been shown that no relation exists between [Ca 2+ ] i and hyperthermic cell killing, although heat‐induced increase of [Ca 2+ ] i can be observed in some cell lines. When ionophores are used, dose‐dependent rises in [Ca 2+ ] i may be found. Beyond a certain threshold of ionophore‐induced increases in [Ca 2+ ] i , cells may be killed. Different threshold levels of [Ca 2+ ] i exist in different cell lines. Hyperthermia can act synergistically with calcium ionophores to potentiate cell killing. Since there is no causal relation between [Ca 2+ ] i and heat toxicity, this synergism can be explained as heat enhanced Ca 2+ toxicity. In the current report, it is shown that both ionophore‐induced Ca 2+ toxicity (37°C) and its potentiation by heat are dependent on extracellular calcium and related to sustained increases in [Ca 2+ ] i . With ionomycin concentrations up to 15 μM, no increase in [Ca 2+ ] i was seen in cells maintained in medium without Ca 2+ . Ionomycin effects on intracellular compartments were absent, and the drug seemed to act solely on the level of the plasmamembrane. Also, the synergism of heat and ionomycin appeared to act at the plasmamembrane, because depletion of extracellular calcium completely abolished this synergistic effect. The data presented are also discussed in the light of controversies existing in the literature for the role of calcium in hyperthermic cell killing. © 1993 Wiley‐Liss, Inc.