MEMBRANE EXCITABILITY AND SECRETION FROM PEPTIDERGIC NERVE-TERMINALS

1. Thin slices of the posterior pituitary can be used as a preparation for the study of biophysical mechanisms underlying neuropeptide secre tion, Patch-clamp techniques in this preparation have revealed the pro perties of ion channels that control the excitability of the nerve ter minal membrane and have clarified the relation between Ca2+ and exocyt osis. 2. Repetitive electrical activity at high frequencies broadens a ction potentials to allow more Ca2+ entry and thus enhance exocytosis, Action potential broadening results from the inactivation of a voltag e-dependent K+ channel, 3. When repetitive electrical activity is sust ained, secretion is depressed, This depression can be attributed in pa rt to action potential failure caused by the opening of a Ca2+-activat ed Kt channel, This channel can be modulated by protein kinases, phosp hatases, and G-proteins, 4. The inhibitory neurotransmitter GABA activ ates a GABAA receptor in the nerve terminal membrane, The gating of th e associated Cl- channel depolarizes the membrane slightly to inactiva te voltage-gated Na+ channels and block action potential propagation, 5 The response of the nerve terminal GABAA receptor is enhanced by neu roactive steroids and this can potentiate the inhibition of neurosecre tion by GABA, The action of neurosteroids at this site could play a ro le in changes in neuropeptide secretion associated with reproductive t ransitions, 6. Ca2+ channels in the nerve terminal membrane are inacti vated by sustained depolarization and by trains of brief pulses, Ca2entry promotes Ca2+ channel inactivation during trains by inhibiting t he recovery of Ca2+ channels from inactivation. The inactivation of Ca 2+ channels can play a role in defining the optimal frequency and trai n duration for evoking neuropeptide secretion. 7. Measurements of memb rane capacitance in peptidergic nerve terminals have revealed rapid ex ocytosis and endocytosis evoked by Ca2+ entry through voltage-gated Ca 2+ channels. Exocytosis is too rapid to account for the delays in neur opeptide secretion evoked by trains of action potentials. Endocytosis sets in rapidly after exocytosis with a time course comparable to that of the rapid endocytosis observed in nerve terminals at rapid synapse s. Our results support the finding in rapid synaptic nerve terminals t hat endocytosis is inhibited by intracellular Ca2+. Multiple pools of vesicles were revealed, and these pools may reflect different stages i n the mobilization and release of neuropeptide.