Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus.

Centre for Research in Neuroscience, Montreal General Hospital and McGill University, Quebec, Canada.
The Journal of Physiology (Impact Factor: 4.38). 07/2004; 557(Pt 3):949-60. DOI: 10.1113/jphysiol.2004.063818
Source: PubMed

ABSTRACT Phasic activity in magnocellular neurosecretory cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials. Dynorphin is copackaged in vasopressin neurosecretory vesicles that are exocytosed from magnocellular neurosecretory cell dendrites and terminals, and both peptides have been implicated in the generation of phasic activity. Here we show that somato-dendritic dynorphin release terminates phasic bursts by autocrine inhibition of plateau potentials in magnocellular neurosecretory cells recorded intracellularly from hypothalamic explants using sharp electrodes. Conditioning spike trains caused an activity-dependent reduction of depolarizing after-potential amplitude that was partially reversed by alpha-latrotoxin (which depletes neurosecretory vesicles) and by nor-binaltorphimine (kappa-opioid receptor antagonist), but not by an oxytocin/vasopressin receptor antagonist or a micro-opioid receptor antagonist, indicating that activity-dependent inhibition of depolarizing after-potentials requires exocytosis of an endogenous kappa-opioid peptide. kappa-Opioid inhibition of depolarizing after-potentials was not mediated by actions on evoked after-hyperpolarizations since these were not affected by kappa-opioid receptor agonists or antagonists. Evoked bursts were prolonged by antagonism of kappa-opioid receptors with nor-binaltorphimine and by depletion of neurosecretory vesicles by alpha-latrotoxin, becoming everlasting in approximately 50% of cells. Finally, spontaneously active neurones exposed to nor-binaltorphimine switched from phasic to continuous firing as plateau potentials became non-inactivating. Thus, dynorphin coreleased with vasopressin generates phasic activity through activity-dependent feedback inhibition of plateau potentials in magnocellular neurosecretory cells.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Structures and property of surfaces are very important in different chemical, physical and biological processes. Understanding the surface characteristics in the microscopic level is essential in order to relate the surface characteristics to the performance of the product. R elation of product performance with surface characteristics helps to improve the product performance through optimizing the manufacturing process. Spatial distribution of surface features which defines the surface characteristics can be captured by the multi-resolution capabilities of wavelet transforms (WT) that can provide not only frequency localization but also spatial localization of feature signatures. A multi-scale molecular simulation can help to investigate the physical and chemical mechanism in the surface. Together with the multi-resolution surface feature analysis, the multi-scale molecular simulation will give a better understanding of the surface phenomena and its relation with the performance matrices. In this paper we discuss the application of this approach for surface characterization of Rh(111) in the adsorption desorption of CO. The adsorption on the surface depends on it s crystal lattice structures and the presence of defects. In the atomic level a first principle density functional theory (DFT) calculation is used to find the adsorption energy. In the mesoscopic level a kinetic Monte Carlo (KMC) model of the surface is used to simulate the temperature programmed desorption (TPD) from the surface. The on-top adsorption energy increases with surface defects in the form of vacancies which shifts the peak maximum of TPD to a higher temperature. To characterize the surface, fractal dimension of the crystal surface is found using wavelet transformation. The fractal dimension of the surface increases with presence of vacancies .
  • [Show abstract] [Hide abstract]
    ABSTRACT: μ-Opioid agonists have no effect on calcium currents (ICa) in neurohypophysial terminals when recorded using the classic whole-cell patch-clamp configuration. However, μ-opioid receptor (MOR)-mediated inhibition of ICa is reliably demonstrated using the perforated-patch configuration. This suggests that the MOR-signaling pathway is sensitive to intraterminal dialysis and is therefore mediated by a readily diffusible second messenger. Using the perforated patch-clamp technique and ratio-calcium-imaging methods, we describe a diffusible second messenger pathway stimulated by the MOR that inhibits voltage-gated calcium channels in isolated terminals from the rat neurohypophysis (NH). Our results show a rise in basal intracellular calcium ([Ca(2+)]i) in response to application of [d-Ala(2)-N-Me-Phe(4),Gly5-ol]-Enkephalin (DAMGO), a MOR agonist, that is blocked by d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a MOR antagonist. Buffering DAMGO-induced changes in [Ca(2+)]i with BAPTA-AM completely blocked the inhibition of both ICa and high-K(+)-induced rises in [Ca(2+)]i due to MOR activation, but had no effect on κ-opioid receptor (KOR)-mediated inhibition. Given the presence of ryanodine-sensitive stores in isolated terminals, we tested 8-bromo-cyclic adenosine diphosphate ribose (8Br-cADPr), a competitive inhibitor of cyclic ADP-ribose (cADPr) signaling that partially relieves DAMGO inhibition of ICa and completely relieves MOR-mediated inhibition of high-K(+)-induced and DAMGO-induced rises in [Ca(2+)]i. Furthermore, antagonist concentrations of ryanodine completely blocked MOR-induced increases in [Ca(2+)]i and inhibition of ICa and high-K(+)-induced rises in [Ca(2+)]i while not affecting KOR-mediated inhibition. Antagonist concentrations of ryanodine also blocked MOR-mediated inhibition of electrically-evoked increases in capacitance. These results strongly suggest that a key diffusible second messenger mediating the MOR-signaling pathway in NH terminals is [Ca(2+)]i released by cADPr from ryanodine-sensitive stores.
    Journal of Neuroscience 03/2014; 34(10):3733-42. · 6.91 Impact Factor
  • Radiotherapy and Oncology 05/2011; 99. · 4.52 Impact Factor

Full-text (2 Sources)

Available from
Oct 14, 2014