Differential inositol 1,4,5-trisphosphate receptor signaling in a neuronal cell line

Abstract

Differential intracellular distribution of the three pharmacologically and biophysically distinct types of IP 3Rs can lead to different subcellular Ca 2+ transients each coupled to discrete intracellular functions. Here, we report the functional localization of differentially distributed IP 3 receptor types in the commonly-used hippocampal cell line HT22. The distinct subcellular localization and Ca 2+ signaling properties of these receptors determine the potential role of specific IP 3 receptor types in cellular function. By utilizing immunochemistry, we conclude that HT22 cells express all three IP 3 receptors with types 1 and 3 being expressed predominantly in the endoplasmic reticulum and perinuclear regions and type 2 being expressed predominantly in the nuclear envelope. Optical imaging studies using the Ca 2+-sensitive indicator dye fluo-3 show that nuclear IP 3 responses have greater amplitude and faster kinetics than cytosolic IP 3 responses corresponding to the biophysical characteristics of the differentially distributed receptor types. These results support the hypothesis that differentially distributed IP 3R isotypes mediate distinct cellular functions through differential, organelle-specific Ca 2+ signaling.