Do submaximal InsP3 concentrations only induce the partial discharge of permeabilized hepatocyte calcium pools because of the concomitant reduction of intraluminal Ca2+ concentration?

Abstract

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 or 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.