Presynaptic calcium channels (original) (raw)
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Functional Specialization of Presynaptic Cav2.3 Ca2+ Channels
Neuron, 2003
Epileptology beit with a lower efficacy than N-and P/Q-type Ca 2ϩ channels . University Bonn Sigmund-Freud Str. 25 In addition to fast neurotransmitter release, some forms of synaptic plasticity also require a rise in presyn-53105 Bonn Germany aptic Ca 2ϩ . At the mossy fiber-CA3 synapse, for instance, the induction of synaptic long-term potentiation 3 Department of Neurophysiology University of Cologne (LTP) appears to be independent of Ca 2ϩ influx into the postsynaptic CA3 neurons (Zalutsky and ). Robert-Koch-Str. 39 50931 Kö ln Rather, a rise in presynaptic Ca 2ϩ is thought to be the initial step in LTP induction (Castillo et al., 1994), which Germany subsequently leads to expression of mossy fiber LTP via an increase in the probability of neurotransmitter release (Zalutsky and Nicoll, 1990; Castillo et al., 2002; Maeda et al., 1997; Xiang et al., 1994; but see Yeckel et Summary al. , 1999). The finding that both fast neurotransmitter release and the induction of mossy fiber LTP require a Ca 2؉ influx into presynaptic terminals via voltagedependent Ca 2؉ channels triggers fast neurotransmitter rise in the presynaptic Ca 2ϩ concentration raises the basic question whether both of these processes are release as well as different forms of synaptic plasticity. Using electrophysiological and genetic techniques triggered by Ca 2ϩ entry via identical Ca 2ϩ channel subtypes. In contrast to the detailed knowledge of Ca 2ϩ we demonstrate that presynaptic Ca 2؉ entry through Ca v 2.3 subunits contributes to the induction of mossy channels mediating fast neurotransmitter release at central synapses (Iwasaki and Takahashi, 1998; Qian and fiber LTP and posttetanic potentiation by brief trains of presynaptic action potentials while they do not play a role in fast synaptic transmission, paired-pulse facilitation, or frequency facilitation. This functional spe-it has remained unclear which Ca 2ϩ entry pathways are a factor in presynaptic forms of LTP. Mossy fiber LTP cialization is most likely achieved by a localization remote from the release machinery and by a Ca v 2.3 can be induced when either N-type or P/Q-type Ca 2ϩ channels are blocked (Castillo et al., 1994), and these channel-dependent facilitation of presynaptic Ca 2؉ influx. Thus, the presence of Ca v 2.3 channels boosts the experiments indicate that-aside from N-and P/Q-type Ca 2ϩ channels-additional sources of Ca 2ϩ entry could accumulation of presynaptic Ca 2؉ triggering presynaptic LTP and posttetanic potentiation without affecting contribute to the induction of LTP. R-type Ca 2ϩ channels resistant to organic Ca 2ϩ chan-the low release probability that is a prerequisite for the enormous plasticity displayed by mossy fiber syn-nel antagonists are present at certain presynaptic terminals and may contribute to intraterminal Ca 2ϩ increases apses.
Presynaptic calcium channels: pharmacology and regulation
Neurochemistry international, 1995
Voltage-dependent Ca2+ channels are considered as molecular trigger elements for signal transmission at chemical synapses. Due to their central role in this fundamental process, function and pharmacology of presynaptic Ca2+ channels have recently been the subject of extensive exploration employing various experimental techniques. Several lines of evidence indicate that, at nerve terminals in higher vertebrates, the evoked influx of Ca2+ -ions is mainly mediated by Ca2+ channels of the P-type. The stringent regulation of presynaptic Ca2+ channels is supposed to be involved in fine-tuning the efficiency of synaptic transmission. Intrinsic control mechanisms, such as voltage- or Ca(2+)-dependent inactivation, or modulation of channel activity, either by G-proteins directly or via phosphorylation by protein kinases, may be of particular functional importance.
Current opinion in neurobiology, 2003
In vertebrates, the physical coupling between presynaptic calcium channels and synaptic vesicle release proteins enhances the efficiency of neurotransmission. Recent evidence indicates that these synaptic proteins may feedback directly on synaptic release by negatively regulating calcium entry, and indirectly through pathways involving second messenger molecules. Studies of individual neurons from both vertebrates and invertebrates have provided novel insights into the roles of scaffolding proteins in calcium channel targeting and neurotransmitter release. These studies require us to expand current models of synaptic transmission. Abbreviations CASK calcium/calmodulin-dependent serine protein kinase CSP cysteine string protein Mint1 munc18-interacting protein PKC protein kinase C SCG superior cervical ganglion synprint synaptic protein interaction site Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery Spafford and Zamponi 309 www.current-opinion.com Current Opinion in Neurobiology 2003, 13:308-314 42. Leveque C, Pupier S, Marqueze B, Geslin L, Kataoka M, Takahashi M, De Waard M, Seagar M: Interaction of cysteine string proteins with the alpha1A subunit of the P/Q-type calcium channel. Enhancement of presynaptic calcium current by cysteine string protein. J Physiol 2002, 538:383-389. 44. Blackmer T, Larsen EC, Takahashi M, Martin TF, Alford S, Hamm HE: G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca 2þ entry. Science 2001, 292:293-297. The authors present evidence that G proteins can regulate synaptic transmission directly and independently of the pathway through the inhibition of N-type calcium channels. This article is complementary to the work of Jarvis et al. [33]
Proceedings of the National Academy of Sciences
Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)–triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short...
Proceedings of the National Academy of Sciences, 2003
Fast cholinergic neurotransmission between superior cervical ganglion neurons (SCGNs) in cell culture is initiated by N-type Ca 2+ currents through Ca v 2.2 channels. To test the ability of different Ca 2+ -channel subtypes to initiate synaptic transmission in these cells, SCGNs were injected with cDNAs encoding Ca v 1.2 channels, which conduct L-type currents, Ca v 2.1 channels, which conduct P/Q-type Ca 2+ currents, and Ca v 2.3 channels, which conduct R-type Ca 2+ currents. Exogenously expressed Ca v 2.1 channels were localized in nerve terminals, as assessed by immunocytochemistry with subtype-specific antibodies, and these channels effectively initiated synaptic transmission. Injection with cDNA encoding Ca v 2.3 channels yielded a lower level of presynaptic labeling and synaptic transmission, whereas injection with cDNA encoding Ca v 1.2 channels resulted in no presynaptic labeling and no synaptic transmission. Our results show that exogenously expressed Ca 2+ channels can med...
Synaptic vesicles: test for a role in presynaptic calcium regulation
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004
Membrane-bound organelles such as mitochondria and the endoplasmic reticulum play an important role in neuronal Ca(2+) homeostasis. Synaptic vesicles (SVs), the organelles responsible for exocytosis of neurotransmitters, occupy more of the volume of presynaptic nerve terminals than any other organelle and, under some conditions, can accumulate Ca(2+). They are also closely associated with voltage-gated Ca(2+) channels (VGCCs) that trigger transmitter release by admitting Ca(2+) into the nerve terminal in response to action potentials (APs). We tested the hypothesis that SVs can modulate Ca(2+) signals in the presynaptic terminal. This has been a difficult question to address because neither pharmacological nor genetic approaches to block Ca(2+) permeation of the SV membrane have been available. To investigate the possible role of SVs in Ca(2+) regulation, we used imaging techniques to compare Ca(2+) dynamics in motor nerve terminals before and after depletion of SVs. We used the tem...
Calcium Channels and Short-term Synaptic Plasticity
Journal of Biological Chemistry, 2013
Voltage-gated Ca 2؉ channels in presynaptic nerve terminals initiate neurotransmitter release in response to depolarization by action potentials from the nerve axon. The strength of synaptic transmission is dependent on the third to fourth power of Ca 2؉ entry, placing the Ca 2؉ channels in a unique position for regulation of synaptic strength. Short-term synaptic plasticity regulates the strength of neurotransmission through facilitation and depression on the millisecond time scale and plays a key role in encoding information in the nervous system. Ca V 2.1 channels are the major source of Ca 2؉ entry for neurotransmission in the central nervous system. They are tightly regulated by Ca 2؉ , calmodulin, and related Ca 2؉ sensor proteins, which cause facilitation and inactivation of channel activity. Emerging evidence reviewed here points to this mode of regulation of Ca V 2.1 channels as a major contributor to short-term synaptic plasticity of neurotransmission and its diversity among synapses. Ca 2ϩ influx through voltage-gated Ca 2ϩ (termed Ca V) channels at presynaptic nerve terminals is an essential step in neurotransmission and plays a crucial role in short-term synaptic plasticity. The Ca V 2 subfamily is predominant in initiating synaptic transmission at fast conventional synapses (1-3). Multiple mechanisms modulate the function of presynaptic Ca V 2 channels and thereby regulate synaptic transmission (2, 4-6). Ca V 2 channels bind the ubiquitous Ca 2ϩ sensor protein calmodulin (CaM) 2 to a site in their C-terminal domain, which induces Ca 2ϩ-dependent facilitation and inactivation of Ca V 2.1 channel activity in response to repetitive stimuli (7-10). Facilitation and inactivation of Ca V 2 channel activity can cause facilitation and depression of synaptic transmission (11, 12). In this minireview, we focus on regulation of the presynaptic Ca V 2 channels by different calcium sensor proteins and the role of this mechanism in short-term synaptic plasticity.
Calcium-induced modulation of synaptic transmission
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 2007
Calcium (Ca 2+ ) is a second messenger regulating a wide variety of intracellular processes. Using GABA-and glycinergic synapses as examples, this review analyzes two functions of this unique ion: postsynaptic Ca 2+ -dependent modulation of receptor-operated channels and Ca 2+ -induced retrograde regulation of neurotransmitter release from the presynaptic terminals. Phosphorylation, rapid Ca 2+ -induced modulation via intermediate Ca 2+ -binding proteins, and changes in the number of functional receptors represent the main pathways of short-and long-term plasticity of postsynaptic receptor-operated channel machinery. Retrograde signaling is an example of synaptic modulation triggered by stimulation of postsynaptic cells and mediated via regulation of presynaptic neurotransmitter release. This mechanism provides postsynaptic neurons with efficient tools to control the presynaptic afferents in an activity-dependent mode. Elevation of intracellular Ca 2+ in a postsynaptic neuron triggers the synthesis of endocannabinoids (derivatives of arachidonic acid). Their retrograde diffusion through the synaptic cleft and consequent activation of presynaptic G-protein coupled to CB1 receptors inhibits the release of neurotransmitter. These mechanisms of double modulation, which include control over the function of postsynaptic ion channels and retrograde suppression of the release machinery, play an important role in Ca 2+ -dependent control of the main excitatory and inhibitory synaptic pathways in the mammalian nervous system.
Cerebral Cortex, 2005
To study the type of presynaptic calcium channels controlling transmitter release at synaptic connections displaying depression or facilitation, dual whole cell recordings combined with biocytin labelling were performed in acute slices from motor cortex of 17-to 22-day-old rats. Layer V postsynaptic interneurons displayed either fast spiking (FS) (n 5 12) or burst firing (BF) (n 5 12) behaviour. The axons of FS cells ramified preferentially around pyramidal cell somata, while BF cell axons ramified predominately around pyramidal cell dendrites. Synapses between pyramidal cells and FS cells displayed brief train depression (n 5 12). Bath application of v-Agatoxin IVA (0.5 mM), blocking P/Q-type calcium channels, decreased mean peak amplitudes of the EPSPs to 40% of control EPSPs (n 5 8). Failure rate of the EPSPs after the first presynaptic action potential increased from 9 6 11 to 28 6 15%. This was associated with an increase in paired pulse ratio of 152 6 44%. v-Conotoxin GVIA (1-10 mM), selectively blocking N-type calcium channels, had no effect on peak amplitudes or frequency dependent properties of these connections (n 5 5). Synapses from pyramidal cells to BF cells displayed brief train facilitation (n 5 8). Application of v-Conotoxin in these connections decreased peak amplitudes of the EPSPs to 15% of control EPSPs (n 5 6) and decreased the paired pulse ratio by 41 6 30%. v-Agatoxin did not have any significant effect on the EPSPs elicited in BF cells. This study indicates that P/Q-type calcium channels are associated with transmitter release at connections displaying synaptic depression, whereas N-type channels are predominantly associated with connections displaying facilitation.
Function and dysfunction of synaptic calcium channels: insights from mouse models
Current Opinion in Neurobiology, 2005
In the past few years several spontaneous or engineered mouse models with mutations in Ca 2+ channel genes have become available, providing a powerful approach to defining Ca 2+ channel function in vivo. There have been recent advances in outlining the phenotypes and in the functional analysis of mouse models with mutations in genes encoding the pore-forming subunits of Ca V 2.1 (P/Q-type), Ca V 2.2 (N-type) and Ca V 2.3 (R-type) Ca 2+ channels, the channels involved in controlling neurotransmitter release at mammalian synapses. These data indicate that Ca V 2.1 channels have a dominant and efficient specific role in initiating fast synaptic transmission at central excitatory synapses in vivo, and suggest that the Ca V 2.1 channelopathies are primarily synaptic diseases. The different disorders probably arise from disruption of neurotransmission in specific brain regions: the cortex in the case of migraine, the thalamus in the case of absence epilepsy and the cerebellum in the case of ataxia.