scholarly journals Intracellular Ca2+Stores and Ca2+Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Michelle D. Amaral ◽  
Lucas Pozzo-Miller
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Trpc Channels ◽  
Styryl Dyes ◽  
Trkb Receptors ◽  
Mepsc Frequency ◽  
Intracellular Ca

Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF application to CA1 pyramidal neurons, the frequency of miniature excitatory postsynaptic currents (mEPSC) increased significantly within 30 seconds; mEPSC amplitude and kinetics were unchanged. This effect was mediated via TrkB receptor activation and required both full intracellular Ca2+stores as well as extracellular Ca2+. Consistent with a role of Ca2+-permeable plasma membrane channels of the TRPC family, the inhibitor SKF96365 prevented the BDNF-induced increase in mEPSC frequency. Furthermore, labeling presynaptic terminals with amphipathic styryl dyes and then monitoring their post-BDNF destaining in slice cultures by multiphoton excitation microscopy revealed that the increase in frequency of mEPSCs reflects vesicular fusion events. Indeed, BDNF application to CA3-CA1 synapses in TTX rapidly enhanced FM1-43 or FM2-10 destaining with a time course that paralleled the phase of increased mEPSC frequency. We conclude that BDNF increases mEPSC frequency by boosting vesicular fusion through a presynaptic, Ca2+-dependent mechanism involving TrkB receptors, Ca2+stores, and TRPC channels.

Role of Ca2+ in the Synchronization of Transmitter Release at Calyceal Synapses in the Auditory System of Rat

2002 ◽  
Vol 87 (1) ◽  
pp. 222-228 ◽  
Author(s):  
Nao Chuhma ◽  
Harunori Ohmori
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Presynaptic Terminal ◽  
Eosin Y ◽  
Early Postnatal Development ◽  
Medial Nucleus ◽  
Combined Application ◽  
Asynchronous Release ◽  
Trapezoid Body

The synchronization of transmitter release in the synapse of the medial nucleus of the trapezoid body (MNTB) is achieved during early postnatal development as a consequence of elimination of delayed asynchronous releases and appears to reflect changes in the dynamics of Ca2+ entry and clearance. To examine the role of Ca2+ in regulating synchronization of transmitter release in the mature synapse (after postnatal day 9, P9), we perturbed Ca2+ dynamics systematically. Replacement of external Ca2+ (2 mM) with Sr2+ induced delayed asynchronous release following the major EPSC. We tried to reproduce asynchronous releases without using Sr2+ and instead by manipulating the time course and the size of Ca2+ transient in the presynaptic terminal, under the assumption that replacement of external Na+ with Li+ or application of eosin-Y would prolong the lifetime of Ca2+ transient by reducing the rate of Ca2+ extrusion from the terminal. With application of Li+, Ca2+ transient in the terminal was prolonged, the EPSC decay time course was prolonged, and the EPSC amplitude increased. However, these EPSCs were not followed by delayed asynchronous release. When Ca2+ influx was reduced, either by partial Ca2+ channel blockade with a low concentration of Cd2+ or ω-agatoxin IVA, a marked asynchronous release resulted. This was further enhanced by the combined application of Li+ or eosin-Y. These results suggest that cooperative increases of both Ca2+ influx and Ca2+ clearance capacities leading to a sharper Ca2+ spike in the presynaptic terminal underlie synchronized transmitter release in the presynaptic terminal of the MNTB.

Calcium transients recorded with arsenazo III in the presynaptic terminal of the squid giant synapse

1981 ◽  
Vol 212 (1187) ◽  
pp. 197-211 ◽  
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Sea Water ◽  
Light Signal ◽  
Presynaptic Terminal ◽  
Arsenazo Iii ◽  
Intracellular Ca ◽  
Squid Giant Synapse ◽  
Giant Synapse ◽  
Light Absorbance

Transient changes in free intracellular Ca 2+ concentration were monitored in the presynaptic terminal of the giant synapse of the squid, by means of the Ca 2+ -sensitive dye arsenazo III. Calibration experiments showed a linear relation between the amount of Ca 2+ injected by iontophoresis into the terminal, and the peak size of the arsenazo light absorbance record. A light signal could be detected on tetanic stimulation of the presynaptic axon bathed in sea water containing 45 mm Ca 2+ . During a 1 s tetanus the light signal rose approximately linearly, even though transmitter release declined rapidly and the light signal subsequently declined with a half-time of 2-6 s. The Ca 2+ transient elicited by single nerve impulses was recorded by signal averaging, and showed a time course very much slower than the duration of transmitter release.

Different VAMP/Synaptobrevin Complexes for Spontaneous and Evoked Transmitter Release at the Crayfish Neuromuscular Junction

1998 ◽  
Vol 80 (6) ◽  
pp. 3233-3246 ◽  
Author(s):  
Shao-Ying Hua ◽  
Dorota A. Raciborska ◽  
William S. Trimble ◽  
Milton P. Charlton
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Neuromuscular Junctions ◽  
Spontaneous Release ◽  
Intracellular Ca ◽  
Crayfish Neuromuscular Junction ◽  
Evoked Transmitter Release

Hua, Shao-Ying, Dorota A. Raciborska, William S. Trimble, and Milton P. Charlton. Different VAMP/synaptobrevin complexes for spontaneous and evoked transmitter release at the crayfish neuromuscular junction. J. Neurophysiol. 80: 3233–3246, 1998. Although vesicle-associated membrane protein (VAMP/synaptobrevin) is essential for evoked neurotransmitter release, its role in spontaneous transmitter release remains uncertain. For instance, many studies show that tetanus toxin (TeNT), which cleaves VAMP, blocks evoked transmitter release but leaves some spontaneous transmitter release. We used recombinant tetanus and botulinum neurotoxin catalytic light chains (TeNT-LC, BoNT/B-LC, and BoNT/D-LC) to examine the role of VAMP in spontaneous transmitter release at neuromuscular junctions (nmj) of crayfish. Injection of TeNT-LC into presynaptic axons removed most of the VAMP immunoreactivity and blocked evoked transmitter release without affecting nerve action potentials or Ca2+ influx. The frequency of spontaneous transmitter release was little affected by the TeNT-LC when the evoked transmitter release had been blocked by >95%. The spontaneous transmitter release left after TeNT-LC treatment was insensitive to increases in intracellular Ca2+. BoNT/B-LC, which cleaves VAMP at the same site as TeNT-LC but uses a different binding site, also blocked evoked release but had minimal effect on spontaneous release. However, BoNT/D-LC, which cleaves VAMP at a different site from the other two toxins but binds to the same position on VAMP as TeNT, blocked both evoked and spontaneous transmitter release at similar rates. The data indicate that different VAMP complexes are employed for evoked and spontaneous transmitter release; the VAMP used in spontaneous release is not readily cleaved by TeNT or BoNT/B. Because the exocytosis that occurs after the action of TeNT cannot be increased by increased intracellular Ca2+, the final steps in neurotransmitter release are Ca2+ independent.

K+ Currents Generated by NMDA Receptor Activation in Rat Hippocampal Pyramidal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2983-2989 ◽  
Author(s):  
Mala M. Shah ◽  
Dennis G. Haylett
Keyword(s):  
Nmda Receptor ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Outward Current ◽  
Receptor Activation ◽  
Bk Channel ◽  
Hippocampal Pyramidal Neurons ◽  
Sk Channel ◽  
Outward Currents ◽  
Nmda Receptor Activation

Long lasting outward currents mediated by Ca2+-activated K+ channels can be induced by Ca2+ influx through N-methyl-d-aspartate (NMDA)-receptor channels in voltage-clamped hippocampal pyramidal neurons. Using specific inhibitors, we have attempted to identify the channels that underlie these outward currents. At a holding potential of −50 mV, applications of 1 mM NMDA to the soma of cultured hippocampal pyramidal neurons induced the expected inward currents. In 44% of cells tested, these were followed by outward currents (average amplitude 60 ± 7 pA) that peaked 2.5 s after the initiation of the inward NMDA currents and decayed with a time constant of 1.4 s. In 43% of those cells exhibiting an outward current, SK channel inhibitors, UCL 1848 (100 nM) and apamin (100 nM) abolished the outward current. In the remainder of the cells, the outward currents were either insensitive or only partly inhibited (44 ± 4%) by 100 nM UCL 1848. In these cells, the outward currents were reduced by the slow afterhyperpolarization (sAHP) inhibitors, muscarine (3 μM; 43 ± 9%), UCL 1880 (3 μM; 34 ± 10%), and UCL 2027 (3 μM; 57 ± 6%). Neither the BK channel inhibitor, charybdotoxin (100 nM), nor the Na+/K+ ATPase inhibitor, ouabain (100 μM), reduced these outward currents. Irrespective of the pharmacology, the time course of the outward current did not differ. Interestingly, no correlation was observed between the presence of a slow apamin-insensitive afterhyperpolarization and an outward current insensitive to SK channel blockers following NMDA-receptor activation. It is concluded that an NMDA-mediated rise in [Ca2+]i can result in the activation of apamin-sensitive SK channels and of the channels that underlie the sAHP. The activation of these channels may, however, depend on their location relative to NMDA receptors as well as on the spatial Ca2+ buffering within individual neurons.

scholarly journals PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels

2014 ◽  
Vol 143 (2) ◽  
pp. 183-201 ◽  
Author(s):  
Kyohei Itsuki ◽  
Yuko Imai ◽  
Hideharu Hase ◽  
Yasushi Okamura ◽  
Ryuji Inoue ◽  
...  
Keyword(s):  
Experimental Data ◽  
Transient Receptor Potential ◽  
Physiological Role ◽  
Receptor Activation ◽  
Pleckstrin Homology Domain ◽  
Peak Time ◽  
Trpc Channels ◽  
Channel Activity ◽  
Open Probability

Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C–insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of total current. In conclusion, our studies demonstrate a fundamental role for PI(4,5)P2 in regulating TRPC6 and TRPC7 activity triggered by PLC-coupled receptor stimulation.

scholarly journals Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury

2005 ◽  
Vol 288 (6) ◽  
pp. H2792-H2801 ◽  
Author(s):  
Vladimir Shneyvays ◽  
Dorit Leshem ◽  
Tova Zinman ◽  
Liaman K. Mamedova ◽  
Kenneth A. Jacobson ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Sodium Azide ◽  
Adenosine Receptor ◽  
Mitochondrial Respiratory Chain ◽  
Receptor Activation ◽  
Atp Level ◽  
Intracellular Ca ◽  
Mitochondrial Respiratory ◽  
In Cells

Activation of either the A1 or the A3 adenosine receptor (A1R or A3R, respectively) elicits delayed cardioprotection against infarction, ischemia, and hypoxia. Mitochondrial contribution to the progression of cardiomyocyte injury is well known; however, the protective effects of adenosine receptor activation in cardiac cells with a respiratory chain deficiency are poorly elucidated. The aim of our study was to further define the role of A1R and A3R activation on functional tolerance after inhibition of the terminal link of the mitochondrial respiratory chain with sodium azide, in a state of normoxia or hypoxia, compared with the effects of the mitochondrial ATP-sensitive K+ channel opener diazoxide. Treatment with 10 mM sodium azide for 2 h in normoxia caused a considerable decrease in the total ATP level; however, activation of adenosine receptors significantly attenuated this decrease. Diazoxide (100 μM) was less effective in protection. During treatment of cultured cardiomyocytes with hypoxia in the presence of 1 mM sodium azide, the A1R agonist 2-chloro- N6-cyclopentyladenosine was ineffective, whereas the A3R agonist 2-chloro- N6-iodobenzyl-5′- N-methylcarboxamidoadenosine (Cl-IB-MECA) attenuated the decrease in ATP level and prevented cell injury. Cl-IB-MECA delayed the dissipation in the mitochondrial membrane potential during hypoxia in cells impaired in the mitochondrial respiratory chain. In cells with elevated intracellular Ca2+ concentration after hypoxia and treatment with NaN3 or after application of high doses of NaN3, Cl-IB-MECA immediately decreased the elevated intracellular Ca2+ concentration toward the diastolic control level. The A1R agonist was ineffective. This may be especially important for the development of effective pharmacological agents, because mitochondrial dysfunction is a leading factor in the pathophysiological cascade of heart disease.

scholarly journals Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability

2020 ◽  
Vol 27 (12) ◽  
pp. 3354-3373
Author(s):  
Fabio Bertan ◽  
Lena Wischhof ◽  
Liudmila Sosulina ◽  
Manuel Mittag ◽  
Dennis Dalügge ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Neuronal Activity ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Excitatory Synapses ◽  
Structural And Functional Properties ◽  
Intracellular Ca ◽  
Memory Acquisition ◽  
Activity Dependent

AbstractDendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca2+ transients trigger signaling cascades that determine the plastic remodeling of dendritic spines, which modulate learning and memory. Here, we study in mice the role of the intracellular Ca2+ channel Ryanodine Receptor 2 (RyR2) in synaptic plasticity and memory formation. We demonstrate that loss of RyR2 in pyramidal neurons of the hippocampus impairs maintenance and activity-evoked structural plasticity of dendritic spines during memory acquisition. Furthermore, post-developmental deletion of RyR2 causes loss of excitatory synapses, dendritic sparsification, overcompensatory excitability, network hyperactivity and disruption of spatially tuned place cells. Altogether, our data underpin RyR2 as a link between spine remodeling, circuitry dysfunction and memory acquisition, which closely resemble pathological mechanisms observed in neurodegenerative disorders.

Role of Membrane Potential in Calcium Signaling During Rhythmic Bursting in Tritonia Swim Interneurons

2007 ◽  
Vol 97 (3) ◽  
pp. 2204-2214 ◽  
Author(s):  
Evan S. Hill ◽  
Paul S. Katz
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Laser Scanning ◽  
Time Course ◽  
Motor Pattern ◽  
Confocal Laser Scanning Microscope ◽  
Confocal Laser ◽  
Intracellular Ca ◽  
Potential Waveform

Rhythmic bursting in neurons is accompanied by dynamic changes in intracellular Ca2+ concentration. These Ca2+ signals may be caused by membrane potential changes during bursting and/or by synaptic inputs. We determined that membrane potential is responsible for most, if not all, of the cytoplasmic Ca2+ signal recorded during rhythmic bursting in two neurons of the escape swim central pattern generator (CPG) of the mollusk, Tritonia diomedea: ventral swim interneuron B (VSI) and cerebral neuron 2 (C2). Ca2+ signals were imaged with a confocal laser scanning microscope while the membrane potential was recorded at the soma. During the swim motor pattern (SMP), Ca2+ signals in both neurons transiently increased during each burst of action potentials with a more rapid decay in secondary than in primary neurites. VSI and C2 were then voltage-clamped at the soma, and each neuron's own membrane potential waveform recorded during the SMP was played back as the voltage command. In all regions of VSI, this completely reproduced the amplitude and time course of Ca2+ signals observed during the SMP, but in C2, the amplitude was lower in the playback experiments than during the SMP, possibly due to space clamp problems. Therefore in VSI, the cytoplasmic Ca2+ signal during the SMP can be accounted for by its membrane potential excursions, whereas in C2 the membrane potential excursions can account for most of the SMP Ca2+ signal.

Inhibition of transmitter release shortens the duration of the excitatory synaptic current at a calyceal synapse

1996 ◽  
Vol 76 (5) ◽  
pp. 3584-3588 ◽  
Author(s):  
T. S. Otis ◽  
L. O. Trussell
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Synaptic Currents ◽  
Quantal Release ◽  
Epsc Amplitude ◽  
Gabaa Receptor Antagonist

1. We investigated the effect of reducing transmitter release on the time course of multiquantal, evoked synaptic currents to test for transmitter “cross talk” between neighboring synaptic release sites within a calyceal synapse. By using a brain slice preparation, neurons in the chick nucleus magnocellularis (nMAG) were voltage clamped and individual presynaptic axons were stimulated to evoke excitatory postsynaptic currents (EPSCs). 2. Application of 100-microM baclofen or 50-microM GABA in the presence of a gamma-aminobutyric acid-A (GABAA) receptor antagonist produced an 85% reduction of EPSCs, consistent with the activation of presynaptic gamma-aminobutyric acid-B (GABAB) receptors. In parallel with the reduction in the amplitude of the EPSC by GABAB receptor activation, the normally strong paired pulse depression (PPD) of the EPSC was converted to facilitation. The reduction in EPSC amplitude by gamma-aminobutyric acid (GABA) or baclofen was accompanied by a 20% reduction in the exponential time constant of decay of the EPSC. Weaker effects on the EPSC time course were observed for synapses with the least PPD. 3. Cd2+ (5 microM), which inhibits presynaptic calcium current, also reduced EPSC amplitude by 85% and converted PPD to facilitation. EPSCs were narrower in Cd2+, though less so than in baclofen. 4. The time course of the EPSC was longer than that of miniature synaptic currents, even after significant block by baclofen, GABA or Cd2+, indicating that dispersion of quantal release may help shape the synaptic waveform. However, the narrowing of the EPSC by baclofen, GABA, and Cd2+ suggests that high levels of quantal release at the calyceal synapse may delay the removal of transmitter, further slowing the EPSC.

Sign in / Sign up

Export Citation Format

Share Document