Spontaneous Ca Influx in Pupal Neurons Is Modulated by IP-Receptor Function and Influences Maturation of the Flight Circuit.

Inositol 1,4,5-trisphosphate receptors (IPR) are Ca channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP-mediated Ca release, and the resulting depletion of the ER store, triggers entry of extracellular Ca by store-operated Ca entry (SOCE). Mutations in IPR attenuate SOCE. Compromised IPR function and SOCE during pupal development of leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development. To understand the effect of compromised IPR function on pupal neuronal calcium signaling, we examined the effects of mutations in the IPR gene () on Ca signals in cultured neurons derived from pupae. We observed increased spontaneous Ca influx across the PM of isolated pupal neurons with mutant IPR and also a loss of SOCE. Both spontaneous Ca influx and reduced SOCE were reversed by over-expression of and , which encode the SOCE Ca channel and the ER Ca-sensor that regulates it, respectively. Expression of voltage-gated Ca channels ( and ) was significantly reduced in mutant neurons. However, expression of mRNAs and transient receptor potential (TRP) protein were increased, suggesting that TRP channels might contribute to the increased spontaneous Ca influx in neurons with mutant IPR. Thus, IPR/SOCE modulates spontaneous Ca influx and expression of PM Ca channels in pupal neurons. Spontaneous Ca influx compensates for the loss of SOCE in mutant neurons.