Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA

Williams, Courtney L.; Chen, Wenyan; Lee, Chia Hsueh; Yaeger, Daniel B.; Vyleta, Nicholas P.; Sa, Smith

doi:10.1038/nn.3162

Cited by 50 publications

(68 citation statements)

References 17 publications

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“…64, which did not find a role for Ca 2+ channels at excitatory cortical synapses). A contribution of spontaneous Ca 2+ channel openings to minis has also been described for inhibitory synapses 65,66 . Therefore, it is important to subdivide 'spontaneous release' into two categories: 63,66 .…”

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confidence: 89%

Molecular mechanisms governing Ca2+ regulation of evoked and spontaneous release

Schneggenburger

Rosenmund

2015

Nat Neurosci

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The relationship between transmitter release evoked by action potentials and spontaneous release has fascinated neuroscientists for half a century, and separate biological roles for spontaneous release are emerging. Nevertheless, separate functions for spontaneous and Ca(2+)-evoked release do not necessarily indicate different origins of these two manifestations of vesicular fusion. Here we review how Ca(2+) regulates evoked and spontaneous release, emphasizing that Ca(2+) can briefly increase vesicle fusion rates one-millionfold above spontaneous rates. This high dynamic range suggests that docked and readily releasable pool (RRP) vesicles might be protected against spontaneous release while also being immediately available for ultrafast Ca(2+)-evoked release. Molecular mechanisms for such release clamping of highly fusogenic RRP vesicles are increasingly investigated. Thus, we view spontaneous release as a consequence of the highly release-competent state of a standing pool of RRP vesicles, which is molecularly fine-tuned to control spontaneous release.

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confidence: 89%

Molecular mechanisms governing Ca2+ regulation of evoked and spontaneous release

Schneggenburger

Rosenmund

2015

Nat Neurosci

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“…The Ca 2+ chelator BAPTA reduces spontaneous release by 95% at cultured hippocampal synapses (186). In addition, antagonists of voltage-gated Ca 2+ channels reduce spontaneous release by ~50% at some synapses (187, 188). At some brain stem neurons, the genetic elimination or blockade of TRPV1 receptors (which are Ca 2+ permeable) eliminates more than 90% of spontaneous release observed in the presence of TTX (189).…”

Section: Spontaneous Releasementioning

confidence: 99%

“…The blockade of voltage-gated Ca 2+ channels did not alter spontaneous inhibitory or excitatory transmission onto CA3 pyramidal cells (192) or excitatory synaptic transmission onto cultured cortical cells (183) and left 50–70% of spontaneous release intact for inhibitory inputs onto hippocampal granule cells (187) and cultured inhibitory synapses (188). Chelating Ca 2+ with BAPTA often leaves a significant fraction of spontaneous release intact.…”

Section: Spontaneous Releasementioning

confidence: 99%

Molecular Mechanisms for Synchronous, Asynchronous, and Spontaneous Neurotransmitter Release

Kaeser

Regehr

2014

Annu. Rev. Physiol.

398

430

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Most neuronal communication relies upon the synchronous release of neurotransmitters, which occurs through synaptic vesicle exocytosis triggered by action potential invasion of a presynaptic bouton. However, neurotransmitters are also released asynchronously with a longer, variable delay following an action potential or spontaneously in the absence of action potentials. A compelling body of research has identified roles and mechanisms for synchronous release, but asynchronous release and spontaneous release are less well understood. In this review, we analyze how the mechanisms of the three release modes overlap and what molecular pathways underlie asynchronous and spontaneous release. We conclude that the modes of release have key fusion processes in common but may differ in the source of and necessity for Ca2+ to trigger release and in the identity of the Ca2+ sensor for release.

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“…Spontaneous release will increase with the number of synaptic contacts, along with other factors including temperature. (b) Exemplary trace of miniature inhibitory postsynaptic currents (mIPSCs) from cortical cultured neurons recorded at −70 mV under previously described conditions (Williams et al, ). Horizontal bars above the trace indicate the traces used in (c) and (d).…”

Section: Introductionmentioning

confidence: 99%

Calcium dependence of spontaneous neurotransmitter release

Williams

2017

J of Neuroscience Research

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Spontaneous release of neurotransmitter is regulated by extracellular [Ca2+] and intracellular [Ca2+]. Curiously, some of the mechanisms of Ca2+ signaling at central synapses are different at excitatory and inhibitory synapses. While the stochastic activity of voltage-activated Ca2+ channels trigger a majority of spontaneous release at inhibitory synapses, this is not the case at excitatory nerve terminals. Ca2+ release from intracellular stores regulates spontaneous release at excitatory and inhibitory terminals, as do agonists of the Ca2+-sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may differ from that underlying evoked release and may be one of the sources of heterogeneity in release mechanisms.

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Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA

Cited by 50 publications

References 17 publications

Molecular mechanisms governing Ca2+ regulation of evoked and spontaneous release

Molecular mechanisms governing Ca2+ regulation of evoked and spontaneous release

Molecular Mechanisms for Synchronous, Asynchronous, and Spontaneous Neurotransmitter Release

Calcium dependence of spontaneous neurotransmitter release

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