PMID- 14645448 OWN - NLM STAT- MEDLINE DCOM- 20041021 LR - 20181113 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 555 IP - Pt 3 DP - 2004 Mar 16 TI - Ca(2+) and frequency dependence of exocytosis in isolated somata of magnocellular supraoptic neurones of the rat hypothalamus. PG - 699-711 AB - In addition to action potential-evoked exocytotic release at neurohypophysial nerve terminals, the neurohormones arginine vasopressin (aVP) and oxytocin (OT) undergo Ca(2+)-dependent somatodendritic release within the supraoptic and paraventricular hypothalamic nuclei. However, the cellular and molecular mechanisms that underlie this release have not been elucidated. In the present study, the whole-cell patch-clamp technique was utilized in combination with high-time-resolved measurements of membrane capacitance (C(m)) and microfluorometric measurements of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) to examine the Ca(2+) and stimulus dependence of exocytosis in the somata of magnocellular neurosecretory cells (MNCs) isolated from rat supraoptic nucleus (SON). Single depolarizing steps (> or =20 ms) that evoked high-voltage-activated (HVA) Ca(2+) currents (I(Ca)) and elevations in intracellular Ca(2+) concentration were accompanied by an increase in C(m) in a majority (40/47) of SON neurones. The C(m) responses were composed of an initial Ca(2+)-independent, transient component and a subsequent, sustained phase of increased C(m) (termed DeltaC(m)) mediated by an influx of Ca(2+), and increased with corresponding prolongation of depolarizing step durations (20-200 ms). From this relationship we estimated the rate of vesicular release to be 1533 vesicles s(-1). Delivery of neurone-derived action potential waveforms (APWs) as stimulus templates elicited I(Ca) and also induced a DeltaC(m), provided APWs were applied in trains of greater than 13 Hz. A train of APWs modelled after the bursting pattern recorded from an OT-containing neurone during the milk ejection reflex was effective in supporting an exocytotic DeltaC(m) in isolated MNCs, indicating that the somata of SON neurones respond to physiological patterns of neuronal activity with Ca(2+)-dependent exocytotic activity. FAU - Soldo, Brandi L AU - Soldo BL AD - Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. FAU - Giovannucci, David R AU - Giovannucci DR FAU - Stuenkel, Edward L AU - Stuenkel EL FAU - Moises, Hylan C AU - Moises HC LA - eng GR - DA 03365/DA/NIDA NIH HHS/United States GR - DA 07268/DA/NIDA NIH HHS/United States GR - T32 DA007268/DA/NIDA NIH HHS/United States GR - R01 NS039914/NS/NINDS NIH HHS/United States GR - NS 39914/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20031128 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 50-56-6 (Oxytocin) RN - SY7Q814VUP (Calcium) SB - IM MH - Action Potentials MH - Animals MH - Calcium/*metabolism MH - Calcium Signaling MH - Cytosol/metabolism MH - Electric Capacitance MH - Electrophysiology MH - Exocytosis/*physiology MH - Fluorometry MH - Lactation/physiology MH - Neurons/metabolism/*physiology MH - Osmolar Concentration MH - Oxytocin/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reaction Time MH - Supraoptic Nucleus/metabolism/*physiology PMC - PMC1664858 EDAT- 2003/12/03 05:00 MHDA- 2004/10/22 09:00 PMCR- 2005/03/16 CRDT- 2003/12/03 05:00 PHST- 2003/12/03 05:00 [pubmed] PHST- 2004/10/22 09:00 [medline] PHST- 2003/12/03 05:00 [entrez] PHST- 2005/03/16 00:00 [pmc-release] AID - jphysiol.2003.051136 [pii] AID - 10.1113/jphysiol.2003.051136 [doi] PST - ppublish SO - J Physiol. 2004 Mar 16;555(Pt 3):699-711. doi: 10.1113/jphysiol.2003.051136. Epub 2003 Nov 28.