[CA2-INDUCED CA2+ RELEASE CAN INVOLVE BOTH IP3-SENSITIVE, AND RYANODINE-SENSITIVE CA2+ RELEASE(](I) ELEVATION EVOKED BY CA2+ READDITION TO THE MEDIUM AFTER AGONIST)

Sustained Ca2+ elevation (''Ca2+ response''), caused by subsequent rea ddition of Ca2+ to the medium after application of adenosine 5'-tripho sphate (ATP, 15 mu M) in a Ca2+-free medium, was studied using single bovine aortic endothelial (BAE) cells. In cells in which the resting i ntracellular Ca2+ concentration ([Ca2+](i)) was between about 50 and 1 10 nM, a massive Ca2+ response occurred and consisted of phasic and su stained components, whereas cells with a resting [Ca2+](i) of over 110 nM displayed small plateau-like Ca2+ responses. An increase of intern al store depletion resulted in loss of the phasic component. When the store was partly depleted, the dependence of the Ca2+ response amplitu de on resting [Ca2+](i) was biphasic over the range of 50 to 110 nM. T he greatest degree of store depletion was associated with small monoph asic Ca2+ responses, the amplitudes of which were almost constant and in the same range as resting [Ca2+](i). Ni2+, known to partly block Ca 2+ entry, caused no change in the half-decay time of [Ca2+](i) down to the level of the sustained phase [57 +/- 3 s in control and 54 +/- 3 s (n = 13) in the presence of 10 mM Ni2+] when added at the peak of th e phasic component of the Ca2+ response. However, it lowered the susta ined phase of the Ca2+ response by 42%. When applied at the start of t he readdition of Ca2+, Ni2+ blocked the phasic component of the Ca2+ r esponse, there being a threefold de crease in the initial rate of [Ca2 +](i) rise. Tn cells with a resting [Ca2+](i) of 75-80 nM, pre-treatme nt with ryanodine (10 mu M) did not affect the peak amplitude of the C a2+ response, but it did increase the level of the sustained component . In some cells, ryanodine caused an oscillatory Ca2+ response. In con clusion, 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 app eared to trigger IP3-sensitive Ca2+ release (IICR) which, in turn, ini tiated Ca2+-sensitive Ca2+ release (CICR), thus resulting in a massive elevation of [Ca2+](i).