SMOOTHLY GRADED CA2-TRISPHOSPHATE-SENSITIVE CA2+ STORES( RELEASE FROMINOSITOL 1,4,5)

Stimulation of cells with Ca2+-mobilizing hormones often leads to the generation of temporally and spatially complex changes in the intracel lular Ca2+ ion concentration ([Ca2+](i)). To understand the mechanisms regulating Ca2+ release from intracellular stores more clearly, we in vestigated the ability of histamine to release Ca2+ stores under diffe rent experimental conditions, using video imaging of single Fura-2-loa ded HeLa cells. In Ca2+-free medium, stepwise increases in histamine c oncentration released an increasing proportion of the intracellular Ca 2+ pool. This pattern of Ca2+-release is analogous to the ''quantal'' release of Ca2+ previously observed using permeabilized cells. Quantal Ca2+ release was observed at both 20 and 37 degrees C and was not due to inactivation or desensitization of the Ca2+ release mechanism, sin ce application of histamine in a pulsatile manner, which avoided desen sitization of the Ca2+-release mechanism, still produced a quantal res ponse. In Ca2+-containing medium at both 20 and 37 degrees C, stepwise increases in histamine concentration evoked [Ca2+](i) responses where the amplitude was smoothly graded in direct proportion to the histami ne concentration. Similar smoothly graded responses were observed from HeLa cells in Ca2+-free medium. These data indicate that hormone-evok ed Ca2+ release from intracellular stores is limited by the hormone co ncentration, and that the mechanisms underlying complex [Ca2+](i) sign als do not lead to an all-or-none release of Ca2+ from the entire intr acellular Ca2+ pool. We suggest that the hormone-sensitive intracellul ar Ca2+ pool is composed of functionally discrete units that are recru ited by agonists in a concentration-dependent manner.