title: [Ca2+]i elevation evoked by Ca2+ readdition to the medium after agonist-induced Ca2+ release can involve both IP3-, and ryanodine-sensitive Ca2+ release.
abstract: Sustained Ca2+ elevation ("Ca2+ response"), caused by subsequent readdition of Ca2+ to the medium after application of adenosine 5'-triphosphate (ATP, 15 microM) in a Ca2+-free medium, was studied using single bovine aortic endothelial (BAE) cells. In cells in which the resting intracellular Ca2+ concentration ([Ca2+]i) was between about 50 and 110 nM, a massive Ca2+ response occurred and consisted of phasic and sustained components, whereas cells with a resting [Ca2+]i of over 110 nM displayed small plateau-like Ca2+ responses. An increase of internal store depletion resulted in loss of the phasic component. When the store was partly depleted, the dependence of the Ca2+ response amplitude on resting [Ca2+]i was biphasic over the range of 50 to 110 nM. The greatest degree of store depletion was associated with small monophasic Ca2+ responses, the amplitudes of which were almost constant and in the same range as resting [Ca2+]i. Ni2+, known to partly block Ca2+ entry, caused no change in the half-decay time of [Ca2+]i down to the level of the sustained phase [57 +/- 4 s in control and 54 +/- 3 s (n = 13) in the presence of 10 mM Ni2+] when added at the peak of the phasic component of the Ca2+ response. However, it lowered the sustained phase of the Ca2+ response by 42%. When applied at the start of the readdition of Ca2+, Ni2+ blocked the phasic component of the Ca2+ response, there being a threefold decrease in the initial rate of [Ca2+]i rise. In cells with a resting [Ca2+]i of 75-80 nM, pre-treatment with ryanodine (10 microM) did not affect the peak amplitude of the Ca2+ response, but it did increase the level of the sustained component. In some cells, ryanodine caused an oscillatory Ca2+ response. In conclusion, partial depletion of the inositol 1,4, 5-trisphosphate-(IP3-) sensitive store by a submaximal concentration of agonist (in Ca2+-free medium) was followed, on readdition of Ca2+, by Ca2+ entry, which appeared to trigger IP3-sensitive Ca2+ release (IICR) which, in turn, initiated Ca2+-sensitive Ca2+ release (CICR), thus resulting in a massive elevation of [Ca2+]i.
authors.affiliation: Department of Physiological Sciences, The Medical School, The University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Mozhayeva
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000819:agonists / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology; D009994:Osmolar Concentration; D012433:Ryanodine / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D012433:Ryanodine; D009532:Nickel; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium