DO SUBMAXIMAL INSP3 CONCENTRATIONS ONLY INDUCE THE PARTIAL DISCHARGE OF PERMEABILIZED HEPATOCYTE CALCIUM POOLS BECAUSE OF THE CONCOMITANT REDUCTION OF INTRALUMINAL CA-2+ CONCENTRATION

In several types of cells whose cytoplasmic Ca2+ is regulated by inositol phosphate derivatives, low concentrations of InsP3 added to permeabilized cell suspensions induce the rapid discharge of part of the InsP3-sensitive Ca2+ pool instead of slow monophasic release of Ca2+ from the entire pool. As a tentative explanation for this puzzling observation, sometimes called 'quantal release', it was suggested that the reduced intraluminal Ca2+ concentration remaining in the Ca2+ pool after a certain amount of Ca2+ had been released might allosterically reduce the channels' affinity for InsP3 and the corresponding InsP3-dependent Ca2+ efflux, and thus result in partial pool discharge (Irvine, R.F. (1990) FEBS Lett. 263. 5 9). We have tested this hypothesis by manipulating the Ca2+ pool contents with ionophore, and found that the rate of InsP3-dependent Ca2+ efflux after ionophore-induced partial discharge of the Ca2+ pools was much faster than what was predicted on the basis of this hypothesis. Heterogeneity of the Ca2+ pools appears to be a more likely reason for the "quantal release' behavior.