Calcium dependence of spontaneous neurotransmitter release

Williams, Courtney L.; Sa, Smith

doi:10.1002/jnr.24116

Cited by 58 publications

(61 citation statements)

References 140 publications

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“…In both cases, similar reductions in Ca 2+ influx would be observed in our presynaptic recordings. Spontaneous release can be regulated independently from evoked release mechanisms ( Kavalali, 2015 ) and does not require VGCCs ( Williams and Smith, 2018 ). Furthermore, their frequency is correlated with the number of AZs that contain fusion-competent SVs ( Kavalali, 2015 ) and changes in post-priming that affect SV fusogenicity, with increased SV fusogenicity correlating with higher spontaneous release rates ( Basu et al, 2007 ).…”

Section: Resultsmentioning

confidence: 99%

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

et al. 2018

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In the presynaptic terminal, the magnitude and location of Ca entry through voltage-gated Ca channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein family at the calyx of Held, a Ca2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the Ca2.1 current density with concomitant reductions in Ca2.1 channel numbers and clusters. Surprisingly, deletion of CAST/ELKS increases release probability while decreasing the readily releasable pool, with no change in active zone ultrastructure. In addition, Ca channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of Ca2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity.

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Section: Resultsmentioning

confidence: 99%

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

et al. 2018

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“…). Although, spontaneous neurotransmitter release events appear to occur randomly, they can nevertheless be regulated by Ca 2+ signals as well as other signal transduction pathways (Glitsch, ; Williams & Smith, ). Interestingly, a key source of Ca 2+ entry for regulation of spontaneous release are voltage‐gated Ca 2+ channel openings that occur at resting membrane potentials, possibly via coordinated opening of multiple Ca 2+ channels.…”

Section: Neuronal Ca2+ Signalling In the Absence Of Activitymentioning

confidence: 99%

Neuronal Ca²⁺ signalling at rest and during spontaneous neurotransmission

Kavalali

2019

The Journal of Physiology

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Action potential driven neuronal signalling drives several electrical and biochemical processes in the nervous system. However, neurons can maintain synaptic communication and signalling under resting conditions independently of activity. Importantly, these processes are regulated by Ca2+ signals that occur at rest. Several studies have suggested that opening of voltage‐gated Ca2+ channels near resting membrane potentials, activation of NMDA receptors in the absence of depolarization or Ca2+ release from intracellular stores can drive neurotransmitter release as well as subsequent signalling in the absence of action potentials. Interestingly, recent studies have demonstrated that manipulation of resting neuronal Ca2+ signalling yielded pronounced homeostatic synaptic plasticity, suggesting a critical role for this resting form of signalling in regulation of synaptic efficacy and neuronal homeostasis. Given their robust impact on synaptic efficacy and neuronal signalling, neuronal resting Ca2+ signals warrant further mechanistic analysis that includes the potential role of store‐operated Ca2+ entry in these processes.

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“…Whether spontaneous vesicle release depends on Ca V 2.x-mediated calcium influx (Kaeser and Regehr, 2014; Williams and Smith, 2018) and whether the same pool of SVs (Groemer and Klingauf, 2007; Ikeda and Bekkers, 2009) or a distinct subset (Fredj and Burrone, 2009) is dedicated to miniature and evoked neurotransmitter release remains under discussion (for review, Truckenbrodt and Rizzoli, 2014). In spite of the controversy, our results demonstrate that the increased frequency of spontaneous release depends on a competent F-actin and intact Ca V α 1 binding site suggesting that close proximity of SVs to Ca V α 1 is required.…”

Section: Discussionmentioning

confidence: 99%

A Tripartite Interaction Among the Calcium Channel α1- and β-Subunits and F-Actin Increases the Readily Releasable Pool of Vesicles and Its Recovery After Depletion

Guzman

Jordan

et al. 2019

Front. Cell. Neurosci.

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Neurotransmitter release is initiated by the influx of Ca 2+ via voltage-gated calcium channels. The accessory β-subunit (Ca V β) of these channels shapes synaptic transmission by associating with the pore-forming subunit (Ca V α 1 ) and up-regulating presynaptic calcium currents. Besides Ca V α 1, Ca V β interacts with several partners including actin filaments (F-actin). These filaments are known to associate with synaptic vesicles (SVs) at the presynaptic terminals and support their translocation within different pools, but the role of Ca V β/F-actin association on synaptic transmission has not yet been explored. We here study how Ca V β 4 , the major calcium channel β isoform in mamalian brain, modifies synaptic transmission in concert with F-actin in cultured hippocampal neurons. We analyzed the effect of exogenous Ca V β 4 before and after pharmacological disruption of the actin cytoskeleton and dissected calcium channel-dependent and -independent functions by comparing the effects of the wild-type subunit with the one bearing a double mutation that impairs binding to Ca V α 1 . We found that exogenously expressed wild-type Ca V β 4 enhances spontaneous and depolarization-evoked excitatory postsynaptic currents (EPSCs) without altering synaptogenesis. Ca V β 4 increases the size of the readily releasable pool (RRP) of SVs at resting conditions and accelerates their recovery after depletion. The enhanced neurotransmitter release induced by Ca V β 4 is abolished upon disruption of the actin cytoskeleton. The Ca V α 1 association-deficient Ca V β 4 mutant associates with actin filaments, but neither alters postsynaptic responses nor the time course of the RRP recovery. Furthermore, this mutant protein preserves the ability to increase the RRP size. These results indicate that the interplay between Ca V β 4 and F-actin also support the recruitment of SVs to the RRP in a Ca V α 1 -independent manner. Our studies show an emerging role of Ca V β in determining SV maturation toward the priming state and its replenishment after release. We envision that this subunit plays a role in coupling exocytosis to endocytosis during the vesicle cycle.

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Calcium dependence of spontaneous neurotransmitter release

Cited by 58 publications

References 140 publications

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

Neuronal Ca²⁺ signalling at rest and during spontaneous neurotransmission

A Tripartite Interaction Among the Calcium Channel α1- and β-Subunits and F-Actin Increases the Readily Releasable Pool of Vesicles and Its Recovery After Depletion

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Calcium dependence of spontaneous neurotransmitter release

Cited by 58 publications

References 140 publications

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

Neuronal Ca2+ signalling at rest and during spontaneous neurotransmission

A Tripartite Interaction Among the Calcium Channel α1- and β-Subunits and F-Actin Increases the Readily Releasable Pool of Vesicles and Its Recovery After Depletion

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Neuronal Ca²⁺ signalling at rest and during spontaneous neurotransmission