Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion

The insulin receptor is a tyrosine kinase receptor that is found in mammalian brain 1 and at high concentrations in the bag cell neurons of Aplysia 2 . We show here that insulin causes an acute rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ) in these neurons and triggers release of neuropeptide. The insulin-sensitive intracellular Ca 2+ pool differs pharmacologically from previously described Ca 2+ stores that are sensitive to inositol trisphosphate and from mitochondrial Ca 2+ stores 3-7 . Insulin, but not thapsigargin, stimulates Ca 2+ release at the distal tips of neurites, the presumed site of neuropeptide secretion 8,9 . The effects of insulin on intracellular Ca 2+ release and neuropeptide secretion occur without triggering spontaneous action potentials. The insulin-sensitive rise in [Ca 2+ ] i moves into the distal tips of neurites after exposure to a cyclic AMP analogue, a treatment that causes a similar translocation of neuronal vesicles 10-12 . Our data indicate that Ca 2+ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide in the absence of neuronal discharge.