Smoothly graded Ca²⁺ release from inositol 1,4,5-trisphosphate-sensitive Ca²⁺ stores

Bootman, Martin D.; Cheek, Tim R.; Moreton, Roger B.; Bennett, Deborah L. and Berridge, Michael J. (1994). Smoothly graded Ca²⁺ release from inositol 1,4,5-trisphosphate-sensitive Ca²⁺ stores. Journal of Biological Chemistry, 269(40) pp. 24783–24791.

URL: http://www.jbc.org/content/269/40/24783.full.pdf+h...

Abstract

Stimulation of cells with Ca²⁺-mobilizing hormones often leads to the generation of temporally and spatially complex changes in the intracellular Ca²⁺ ion concentration ([Ca²⁺]_i). To understand the mechanisms regulating Ca²⁺ release from intracellular stores more clearly, we investigated the ability of histamine to release Ca²⁺ stores under different experimental conditions, using video imaging of single Fura-2-loaded HeLa cells. In Ca²⁺-free medium, stepwise increases in histamine concentration released an increasing proportion of the intracellular Ca²⁺ 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 °C and was not due to inactivation or desensitization of the Ca²⁺ release mechanism, since application of histamine in a pulsatile manner, which avoided desensitization of the Ca²⁺-release mechanism, still produced a quantal response. In Ca²⁺-containing medium at both 20 and 37 °C, stepwise increases in histamine concentration evoked [Ca²⁺]_i responses where the amplitude was smoothly graded in direct proportion to the histamine concentration. Similar smoothly graded responses were observed from HeLa cells in Ca²⁺-free medium. These data indicate that hormone-evoked Ca²⁺ release from intracellular stores is limited by the hormone concentration, and that the mechanisms underlying complex [Ca²⁺]_i signals do not lead to an all-or-none release of Ca²⁺ from the entire intracellular Ca²⁺ pool. We suggest that the hormone-sensitive intracellular Ca²⁺ pool is composed of functionally discrete units that are recruited by agonists in a concentration-dependent manner.

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