Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells.
Calcium ionophores are generally assumed to directly facilitate the transport of Ca2+ across the plasma membrane. The ability of Ca2+ ionophores ionomycin and A23187 to increase Ca2+ concentration in the cytosol ([Ca2+]i) in different cells was analyzed in detail using fluorescent Ca2+ probes. In fura-2-loaded cells, the dependence of the level of [Ca2+]i on ionomycin and A23187 concentrations had a complex character and could not be explained by ionophoric properties only. The Ca2+ signal induced by the Ca2+ ionophores consisted of three components. The first component was due to the activation of Ca2+ influx through native Ca2+ channels and was sensitive to drugs which inhibited the receptor-operated Ca2+ influx. The second component originated from phospholipase C-dependent mobilization of Ca2+ from intracellular stores. An additional influx of Ca2+ into the cells was activated in this case by a store-regulated mechanism. The third ionophoric component was very small at low concentrations of the ionophores. The effect of the ionophores on Ca2+ influx and Ca2+ mobilization was demonstrated on different cells such as Ehrlich ascites tumour cells, murine peritoneal neutrophils, macrophages, and T-lymphocytes. Thymocytes, neutrophils, and Ehrlich ascites tumour cells were more sensitive to the Ca2+ ionophores. Memory T-cells and brown preadipocytes were ionophore-resistant. The insensitivity to Ca2+ ionophores correlated with the absence of Ca2+ in the intracellular Ca2+ stores and the low activity of plasma membrane store-regulated Ca2+ channels.
Dedkova
E N
EN
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region.
Sigova
A A
AA
Zinchenko
V P
VP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology*; D051379:Mice; D051381:Rats
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D007476:Ionophores; D002118:Calcium