Compensation of inositol 1,4,5-trisphosphate receptor function by altering sarco-endoplasmic reticulum calcium ATPase activity in the Drosophila flight circuit

Abstract

Ionic Ca²⁺ functions as a second messenger to control several intracellular processes. It also influences intercellular communication. The release of Ca²⁺ from intracellular stores through the inositol 1,4,5-trisphosphate receptor (InsP₃R) occurs in both excitable and nonexcitable cells. In Drosophila, InsP₃R activity is required in aminergic interneurons during pupal development for normal flight behavior. By altering intracellular Ca²⁺ and InsP₃ levels through genetic means, we now show that signaling through the InsP₃R is required at multiple steps for generating the neural circuit required in air puff-stimulated Drosophila flight. Decreased Ca²⁺ release in aminergic neurons during development of the flight circuit can be compensated by reducing Ca²⁺ uptake from the cytosol to intracellular stores. However, this mode of increasing intracellular Ca²⁺ is insufficient for maintenance of flight patterns over time periods necessary for normal flight. Our study suggests that processes such as maintenance of wing posture and formation of the flight circuit require InsP₃ receptor function at a slow timescale and can thus be modulated by altering levels of cytosolic Ca²⁺ and InsP₃. In contrast, maintenance of flight patterns probably requires fast modulation of Ca²⁺ levels, in which the intrinsic properties of the InsP₃R play a pivotal role.