{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:17:00Z","timestamp":1761920220958,"version":"3.37.3"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,5,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The intracellular concentration of free calcium ions ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in a nerve terminal controls both transmitter release and synaptic plasticity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The rapid triggering of transmitter release depends on the local micro\u2010 or nanodomain of highly elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in the vicinity of open voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channels, whereas short\u2010term synaptic plasticity is often controlled by global changes in residual [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, averaged over the whole nerve terminal volume.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here we describe dynamic changes of such global [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in the calyx of Held \u2013 a giant mammalian glutamatergic nerve terminal, which is particularly suited for biophysical studies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We provide quantitative data on Ca<jats:sup>2+<\/jats:sup> inflow, Ca<jats:sup>2+<\/jats:sup> buffering and Ca<jats:sup>2+<\/jats:sup> clearance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data allow us to predict changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in the nerve terminal in response to a wide range of stimulus protocols at high temporal resolution and provide a basis for the modelling of short\u2010term plasticity of glutamatergic synapses.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Many aspects of short\u2010term synaptic plasticity (STP) are controlled by relatively slow changes in the presynaptic intracellular concentration of free calcium ions ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) that occur in the time range of a few milliseconds to several seconds. In nerve terminals, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> equilibrates diffusionally during such slow changes, such that the globally measured, residual [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> that persists after the collapse of local domains is often the appropriate parameter governing STP. Here, we study activity\u2010dependent dynamic changes in global [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> at the rat calyx of Held nerve terminal in acute brainstem slices using patch\u2010clamp and microfluorimetry. We use low concentrations of a low\u2010affinity Ca<jats:sup>2+<\/jats:sup> indicator dye (100\u00a0\u03bc<jats:sc>m<\/jats:sc> Fura\u20106F) in order not to overwhelm endogenous Ca<jats:sup>2+<\/jats:sup> buffers. We first study voltage\u2010clamped terminals, dialysed with pipette solutions containing minimal amounts of Ca<jats:sup>2+<\/jats:sup> buffers, to determine Ca<jats:sup>2+<\/jats:sup> binding properties of endogenous fixed buffers as well as the mechanisms of Ca<jats:sup>2+<\/jats:sup> clearance. Subsequently, we use pipette solutions including 500\u00a0\u03bc<jats:sc>m<\/jats:sc> EGTA to determine the Ca<jats:sup>2+<\/jats:sup> binding kinetics of this chelator. We provide a formalism and parameters that allow us to predict [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> changes in calyx nerve terminals in response to a wide range of stimulus protocols. Unexpectedly, the Ca<jats:sup>2+<\/jats:sup> affinity of EGTA under the conditions of our measurements was substantially lower (<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>\u00a0=\u00a0543\u00a0\u00b1\u00a051\u00a0n<jats:sc>m<\/jats:sc>) than measured <jats:italic>in vitro<\/jats:italic>, mainly as a consequence of a higher than previously assumed dissociation rate constant (2.38\u00a0\u00b1\u00a00.20 s<jats:sup>\u22121<\/jats:sup>), which we need to postulate in order to model the measured presynaptic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transients.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272773","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T06:26:39Z","timestamp":1481610399000},"page":"3219-3236","source":"Crossref","is-referenced-by-count":21,"title":["Dynamics of volume\u2010averaged intracellular Ca<sup>2+<\/sup> in a rat CNS nerve terminal during single and repetitive voltage\u2010clamp depolarizations"],"prefix":"10.1113","volume":"595","author":[{"given":"Kun\u2010Han","family":"Lin","sequence":"first","affiliation":[{"name":"Emeritus Group Membrane Biophysics Max Planck Institute for Biophysical Chemistry  37077 G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Taschenberger","sequence":"additional","affiliation":[{"name":"Emeritus Group Membrane Biophysics Max Planck Institute for Biophysical Chemistry  37077 G\u00f6ttingen Germany"},{"name":"Department of Molecular Neurobiology Max Planck Institute of Experimental Medicine  37075 G\u00f6ttingen Germany"},{"name":"DFG\u2010Research Centre for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)  37073 G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-7922","authenticated-orcid":false,"given":"Erwin","family":"Neher","sequence":"additional","affiliation":[{"name":"Emeritus 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