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      Electrical Membrane Activity and Intracellular Calcium Buffering Control Exocytosis Efficiency in Xenopus Melanotrope Cells

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          In neural and neuroendocrine cells, Ca<sup>2+</sup> influx is essential for exocytosis. Ca<sup>2+</sup> influx takes place through electrical membrane activity, which often occurs in bursts of action potentials that lead to intracellular Ca<sup>2+</sup> oscillations. Cytoplasmic Ca<sup>2+</sup> buffers and intracellular Ca<sup>2+</sup> stores are involved in the propagation of the oscillations through the cell. Studies focused on action potential bursts with a high frequency up to 20 Hz indicate that, depending on the cell type under investigation, bursts either enhance or reduce exocytosis efficiency. In many cell types, the bursting frequency can be as low as 1 Hz, although no information is present on whether this influences exocytosis efficiency. The present study addresses the role of low-frequency bursts around 1 Hz and cytoplasmic Ca<sup>2+</sup> buffering in the regulation of exocytosis efficiency, using neuroendocrine melanotrope cells of the amphibian Xenopus laevis. Exocytosis efficiency was determined by membrane capacitance measurements. Mimicking the bursting activity of 1 Hz (typical for this cell type) by repetitive depolarizing pulses enhanced exocytosis efficiency by 58% compared to application of only one single depolarizing pulse. This increase appears to be particularly due to a small number of distinct depolarizing pulses within a burst. Including the fast Ca<sup>2+</sup> buffer BAPTA in the intracellular solution reduced exocytosis efficiency by 60% in the first part of a burst, whereas during the later part of the burst, stimulation (+50%) took place. We conclude that low-frequency bursting in the Xenopus melanotrope cell strongly promotes exocytosis efficiency and that this efficiency also depends on the capacity of the cytoplasm to buffer the intracellular Ca<sup>2+</sup> signal; strong Ca<sup>2+</sup> buffering during a short burst will decrease exocytosis efficiency, whereas with prolonged bursts, buffering capacity will be overcome, leading to Ca<sup>2+</sup> accumulation and thus enhanced exocytosis efficiency.

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          Most cited references 12

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          Ca2+ binding to synaptotagmin: how many Ca2+ ions bind to the tip of a C2-domain?

          C2-domains are widespread protein modules with diverse Ca2+-regulatory functions. Although multiple Ca2+ ions are known to bind at the tip of several C2-domains, the exact number of Ca2+-binding sites and their functional relevance are unknown. The first C2-domain of synaptotagmin I is believed to play a key role in neurotransmitter release via its Ca2+-dependent interactions with syntaxin and phospholipids. We have studied the Ca2+-binding mode of this C2-domain as a prototypical C2-domain using NMR spectroscopy and site-directed mutagenesis. The C2-domain is an elliptical module composed of a beta-sandwich with a long axis of 50 A. Our results reveal that the C2-domain binds three Ca2+ ions in a tight cluster spanning only 6 A at the tip of the module. The Ca2+-binding region is formed by two loops whose conformation is stabilized by Ca2+ binding. Binding involves one serine and five aspartate residues that are conserved in numerous C2-domains. All three Ca2+ ions are required for the interactions of the C2-domain with syntaxin and phospholipids. These results support an electrostatic switch model for C2-domain function whereby the beta-sheets of the domain provide a fixed scaffold for the Ca2+-binding loops, and whereby interactions with target molecules are triggered by a Ca2+-induced switch in electrostatic potential.
            • Record: found
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            Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice.

            Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergic neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of starvation by 4 weeks of age. We used gene therapy to ascertain where DA replacement in the brain restores feeding and other behaviors in DD mice. Restoration of DA production within the caudate putamen restores feeding on regular chow and nest-building behavior, whereas restoration of DA production in the nucleus accumbens restores exploratory behavior. Replacement of DA to either region restores preference for sucrose or a palatable diet without fully rescuing coordination or initiation of movement. These data suggest that a fundamental difference exists between feeding for sustenance and the ability to prefer rewarding substances.
              • Record: found
              • Abstract: not found
              • Article: not found

              Exocytosis: a molecular and physiological perspective.

               Jane Zucker (1996)

                Author and article information

                S. Karger AG
                March 2003
                03 April 2003
                : 77
                : 3
                : 153-161
                Department of Cellular Animal Physiology, Institute of Cellular Signalling and Nijmegen Institute for Neurosciences, University of Nijmegen, Nijmegen, The Netherlands
                69506 Neuroendocrinology 2003;77:153–161
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 42, Pages: 9
                Cellular Neuroendocrinology


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