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The Journal of Neuroscience, February 4, 2004, 24(5):1226-1235; doi:10.1523/JNEUROSCI.4286-03.2004

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Cellular/Molecular
Ca²⁺ Syntillas, Miniature Ca²⁺ Release Events in Terminals of Hypothalamic Neurons, Are Increased in Frequency by Depolarization in the Absence of Ca²⁺ Influx

Valérie De Crescenzo,¹ Ronghua ZhuGe,^1,2 Cristina Velázquez-Marrero,¹ Lawrence M. Lifshitz,^1,2 Edward Custer,¹ Jeffrey Carmichael,² F. Anthony Lai,³ Richard A. Tuft,^1,2 Kevin E. Fogarty,^1,2 José R. Lemos,¹ and John V. Walsh, Jr¹

¹Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, ²Biomedical Imaging Group, University of Massachusetts Medical School, Worcester, Massachusetts 01605, and ³ Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom

Localized, brief Ca²⁺ transients (Ca²⁺ syntillas) caused by release from intracellular stores were found in isolated nerve terminals from magnocellular hypothalamic neurons and examined quantitatively using a signal mass approach to Ca²⁺ imaging. Ca²⁺ syntillas (scintilla, L., spark, from a synaptic structure, a nerve terminal) are caused by release of 250,000 Ca ions on average by a Ca²⁺ flux lasting on the order of tens of milliseconds and occur spontaneously at a membrane potential of –80 mV. Syntillas are unaffected by removal of extracellular Ca²⁺, are mediated by ryanodine receptors (RyRs) and are increased in frequency, in the absence of extracellular Ca²⁺, by physiological levels of depolarization. This represents the first direct demonstration of mobilization of Ca²⁺ from intracellular stores in neurons by depolarization without Ca²⁺ influx. The regulation of syntillas by depolarization provides a new link between neuronal activity and cytosolic [Ca²⁺] in nerve terminals.

Key words: calcium imaging; calcium spark; intracellular calcium; neurosecretion; presynaptic; ryanodine receptor

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Received Sep 20, 2003; revised December 9, 2003; accepted December 11, 2003.

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