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

Abstract

The insulin receptor is a tyrosine kinase receptor that is found in mammalian brain¹ and at high concentrations in the bag cell neurons of Aplysia². We show here that insulin causes an acute rise in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in these neurons and triggers release of neuropeptide. The insulin-sensitive intracellular Ca²⁺ pool differs pharmacologically from previously described Ca²⁺ stores that are sensitive to inositol trisphosphate and from mitochondrial Ca²⁺ stores^3–7. Insulin, but not thapsigargin, stimulates Ca²⁺ release at the distal tips of neurites, the presumed site of neuropeptide secretion^8,9. The effects of insulin on intracellular Ca²⁺ release and neuropeptide secretion occur without triggering spontaneous action potentials. The insulin-sensitive rise in [Ca²⁺]_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 Ca²⁺ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide in the absence of neuronal discharge.