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Actions of ionomycin, 4-BrA23187 and a novel electrogenic Ca2+ ionophore on mitochondria in intact cells

Abramov, AY; Duchen, MR; (2003) Actions of ionomycin, 4-BrA23187 and a novel electrogenic Ca2+ ionophore on mitochondria in intact cells. CELL CALCIUM , 33 (2) 101 - 112.

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Abstract

We have used fluorescence digital imaging techniques to explore the actions of two groups of Ca2+ ionophores: (i) ferutinin, an electrogenic naturally occurring ionophore, and (ii) the neutral ionophores 4-BrA23187 and ionomycin, on cytosolic [Ca2+] ([Ca2+](c)), mitochondrial [Ca2+] ([Ca2+](m)) and mitochondrial membrane potential (Deltapsim) in HepG2 cells and primary hippocampal neurones in culture. 4-BrA23187 and ionomycin promoted the equilibration of [Ca (2+)] gradients between cellular compartments, including ER, mitochondria and cytosol. Thus, [Ca2+](c) and [Ca2+]m increased together and then recovered in parallel on removal of the ionophore. In contrast, following a rise in [Ca2+], in response to ferutinin, [Ca2+] remained elevated for prolonged periods after the recovery of [Ca2+](c) levels despite washout of the compound. Both groups of Ca2+ ionophores caused some mitochondrial depolarisation, although this was highly variable in degree. Mitochondrial depolarisation induced by ionomycin and 4-BrA23187 was often modest, independent of cyclosporin A (CsA), was suppressed in the absence of extracellular Ca2+ and was enhanced by pre-incubation of cells with the inhibitor of the mitochondrial Ca2+/2Na(+)-exchanger, CGP37157, suggesting that the change in potential reflects the prior state of mitochondrial calcium loading. The mitochondrial depolarisation induced by ferutinin was not influenced by CGP37157 but was completely blocked by CsA, suggesting that it reflects opening of the mitochondrial permeability transition pore (mPTP). We suggest that ferutinin may provide a very valuable tool to promote mitochondrial calcium overload experimentally and to promote calcium-dependent opening of the mPTP. (C) 2003 Elsevier Science Ltd. All rights reserved.

Type: Article
Title: Actions of ionomycin, 4-BrA23187 and a novel electrogenic Ca2+ ionophore on mitochondria in intact cells
Keywords: lonophore, calcium, mitochondria, ferutinin, ionomycin, PERMEABILITY TRANSITION, HIPPOCAMPAL-NEURONS, IN-SITU, TRANSPORT, MEMBRANE, DEATH, LYMPHOCYTES, INHIBITION, ASTROCYTES, ACTIVATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/149449
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