INSULIN-RECEPTOR IN APLYSIA NEURONS - CHARACTERIZATION, MOLECULAR-CLONING, AND MODULATION OF ION CURRENTS

We have isolated the cDNA for a tyrosine kinase receptor that is expre ssed in the nervous system of Aplysia californica and that is similar to the vertebrate insulin receptor. Binding studies and immunocytochem ical staining show that the receptor is abundant in the bag cell neuro ns. Application of vertebrate insulin to clusters of bag cell neurons stimulates the phosphorylation of the receptor on tyrosine residues, a nd exposure of isolated bag cell neurons to insulin produces an increa se in height and a decrease in duration of the action potentials that can be detected within 15-30 min. These effects were not seen with ins ulin-like growth factor-1. In voltage-clamped neurons, insulin produce s an increase in the amplitude of the voltage-dependent Ca2+ current t hat can be blocked by preincubation with herbimycin A, an inhibitor of tyrosine kinases. Insulin also enhances a delayed K+ current, We sugg est that insulin-like peptides regulate the excitability of the bag ce ll neurons.