title: Post-afterdischarge depolarization does not stimulate prolonged neurohormone secretion but is required for activity-dependent stimulation of neurohormone biosynthesis from peptidergic neurons.
abstract: Membrane depolarization plays a critical role in stimulating secretion of neuropeptides and can also be important in regulating transcriptional and translational events that control peptide biosynthesis. The purpose of this study was to test the hypothesis that persistent membrane depolarization after the end of an electrical afterdischarge plays an important role in stimulating both prolonged secretion of egg-laying hormone (ELH) and ELH synthesis from peptidergic bag cell neurons of Aplysia. Experimental preparations were treated with a low Na(+) solution to rapidly repolarize membrane potential (Vm). Compared with control preparations, the low Na(+) solution caused rapid membrane repolarization to resting levels, significant shortening of the duration of the afterdischarge, and significant decrease in the decay time constant of cytosolic Ca(2+) ([Ca(2+)](i)) concentrations, but no effect on peak [Ca(2+)](i), total [Ca(2+)](i) above baseline, or duration of elevated [Ca(2+)](i). Contrary to both theoretical expectations and findings in other cell types, low Na(+) treatment and the resulting premature repolarization of Vm did not inhibit ELH secretion. On the other hand, low Na(+) treatment that blocked prolonged depolarization, as well as inhibition of Ca(2+) influx, prevented the afterdischarge-induced stimulation of ELH synthesis. These findings provide support for membrane depolarization acting as a trigger mechanism, rather than a sustained driving force, for cellular events that control ELH secretion. It also demonstrates, for the first time, a critical role for postdischarge Vm in regulating an important aspect of neuroendocrine cell function-that of hormone synthesis.
authors.affiliation: Department of Physiology, David Geffen School of Medicine at University of California-Los Angeles, 90095-1751, USA. nwayne@mednet.ucla.edu
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Wayne
authors.forename: Wenjau
authors.initials: W
authors.lastname: Lee
authors.forename: Stephan
authors.initials: S
authors.lastname: Michel
authors.forename: Sarah Buxton
authors.initials: SB
authors.lastname: De Quintana
mesh_terms: D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007447:Invertebrate Hormones / Q000096:biosynthesis / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D009994:Osmolar Concentration; D012964:Sodium / Q000008:administration & dosage
chemical_list: D007447:Invertebrate Hormones; D009479:Neuropeptides; C026880:egg-laying hormone, Mollusca; D012964:Sodium; D002118:Calcium