Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

2006 ◽  
Vol 96 (3) ◽  
pp. 1267-1277 ◽  
Author(s):  
Alexander Fisyunov ◽  
Vera Tsintsadze ◽  
Rogier Min ◽  
Nail Burnashev ◽  
Natalia Lozovaya
Keyword(s):  
Calcium Influx ◽  
Direct Action ◽  
Similar Efficacy ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Calcium Currents ◽  
Purkinje Neurons ◽  
Presynaptic Calcium ◽  
Central Synapses ◽  
P Type

Endocannabinoids released by postsynaptic cells inhibit neurotransmitter release in many central synapses by activating presynaptic cannabinoid CB1 receptors. In particular, in the cerebellum, endocannabinoids inhibit synaptic transmission at granule cell to Purkinje cell synapses by modulating presynaptic calcium influx via N-, P/Q-, and R-type calcium channels. Using whole cell patch-clamp techniques, we show that in addition to this presynaptic action, both synthetic and endogenous cannabinoids inhibit P-type calcium currents in isolated rat Purkinje neurons independent of CB1 receptor activation. The IC50 for the anandamide (AEA)-induced inhibition of P-current peak amplitude was 1.04 ± 0.04 μM. In addition, we demonstrate that all the tested cannabinoids in a physiologically relevant range of concentrations strongly accelerate inactivation of P currents. The effects of AEA cannot be attributed to the metabolism of AEA because a nonhydrolyzing analogue of AEA, methanandamide inhibited P-type currents with a similar efficacy. All effects of cannabinoids on P-type Ca2+ currents were insensitive to antagonists of CB1 cannabinoid or vanilloid TRPV1 receptors. In cerebellar slices, WIN 55,212–2 significantly affected spontaneous firing of Purkinje neurons in the presence of CB1 receptor antagonist, in a manner similar to that of a specific P-type channel antagonist, indicating a possible functional implication of the direct effects of cannabinoids on P current. Taken together these findings demonstrate a functionally important direct action of cannabinoids on P-type calcium currents.

scholarly journals Effect of changes in action potential shape on calcium currents and transmitter release in a calyx–type synapse of the rat auditory brainstem

1999 ◽  
Vol 354 (1381) ◽  
pp. 347-355 ◽  
Author(s):  
J. G. G. Borst ◽  
B. Sakmann
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Time Course ◽  
Calcium Influx ◽  
Auditory Brainstem ◽  
Calcium Currents ◽  
Medial Nucleus ◽  
Potential Shape ◽  
Presynaptic Calcium ◽  
Rat Brainstem

We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medial nucleus of the trapezoid body, in slices of the rat brainstem. Calyces were voltage clamped with different action potential waveforms. The amplitude of the excitatory postsynaptic currents depended supralinearly on the size of the calcium influx, in the absence of changes in the time–course of the calcium influx. This result is in agreement with the view thact at this synapse most vesicles are released by the combined action of multiple calcium channels.

An Increase in Calcium Influx Contributes to Post-Tetanic Potentiation at the Rat Calyx of Held Synapse

2006 ◽  
Vol 96 (6) ◽  
pp. 2868-2876 ◽  
Author(s):  
Ron L. P. Habets ◽  
J. Gerard G. Borst
Keyword(s):  
Action Potential ◽  
Calcium Influx ◽  
Calcium Currents ◽  
Calyx Of Held ◽  
Calcium Buffer ◽  
Whole Cell Patch Clamp ◽  
Auditory Brain Stem ◽  
Post Tetanic Potentiation ◽  
Presynaptic Calcium ◽  
Fluorescence Transients

We studied the contribution of a change in presynaptic calcium influx to posttetanic potentiation (PTP) in the calyx of Held synapse, an axosomatic synapse in the auditory brain stem. We made whole cell patch-clamp recordings of a principal cell after loading of the presynaptic terminal with a calcium dye. After induction of PTP by a high-frequency train of afferent stimuli, the Fluo-4 fluorescence transients evoked by an action potential became on average 15 ± 4% larger ( n = 7). Model predictions did not match the fluorescence transients evoked by trains of brief calcium currents unless the endogenous calcium buffer had low affinity for calcium, making a contribution of saturation of the endogenous buffer to the synaptic potentiation we observed in the present experiments less likely. Our data therefore suggest that the increase of release probability during PTP at the calyx of Held synapse is largely explained by an increase in the calcium influx per action potential.

Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin

2013 ◽  
Vol 110 (9) ◽  
pp. 2071-2081 ◽  
Author(s):  
Tyler W. Dunn ◽  
Wayne S. Sossin
Keyword(s):  
Calcium Current ◽  
Kinase Inhibitors ◽  
Calcium Influx ◽  
Receptor Activation ◽  
Calcium Currents ◽  
Src Tyrosine Kinase ◽  
Nociceptive Neurons ◽  
Readily Releasable Pool ◽  
G Protein Coupled ◽  
Calcium Secretion

The inhibition of Aplysia pleural mechanosensory neuron synapses by dopamine and serotonin through activation of endogenous dopaminergic and expressed 5-HT1Apl(a)/b receptors, respectively, involves a reduction in action potential-associated calcium influx. We show that the inhibition of synaptic efficacy is downstream of the readily releasable pool, suggesting that inhibition is at the level of calcium secretion coupling, likely a result of the changes in the calcium current. Indeed, the inhibitory responses directly reduce a CaV2-like calcium current in isolated sensory neurons. The inhibition of the calcium current is voltage independent as it is not affected by a strong depolarizing prepulse, consistent with other invertebrate CaV2 calcium currents. Similar to voltage-independent inhibition of vertebrate nociceptors, inhibition was blocked with Src tyrosine kinase inhibitors. The data suggest a conserved mechanism by which G protein-coupled receptor activation can inhibit the CaV2 calcium current in nociceptive neurons.

Biphasic action of axonal GABA-A receptors on presynaptic calcium influx

2011 ◽  
Vol 105 (6) ◽  
pp. 2931-2936 ◽  
Author(s):  
Brandon M. Stell
Keyword(s):  
Action Potential ◽  
Cerebellar Cortex ◽  
High Speed ◽  
Calcium Influx ◽  
Receptor Activation ◽  
Aminobutyric Acid ◽  
Parallel Fibers ◽  
Gaba A ◽  
Biphasic Effect ◽  
Presynaptic Calcium

Although ionotropic γ-aminobutyric acid A receptors (GABAARs) have long been known to exist on the axons of many different cells, their effect on axon excitability and synaptic transmission remains controversial. Here, using high-speed Ca2+ imaging, it is shown that they induce a biphasic effect in parallel fibers of the cerebellar cortex. Multicellular measurements indicate a facilitation of action potential (AP)-evoked Ca2+ transients, which is subsequently followed by depression. However, the receptor activation does not increase influx of Ca2+ into individual fibers but instead, increases the probability of AP generation. These results provide a description of the effect of presynaptic GABAAR activation and explain why reports of the effect of their activation have been so varied.

scholarly journals Activation of Neuronal Nicotinic Receptors Inhibits Acetylcholine Release in the Neuromuscular Junction by Increasing Ca2+ Flux through Cav1 Channels

2021 ◽  
Vol 22 (16) ◽  
pp. 9031
Author(s):  
Nikita Zhilyakov ◽  
Arsenii Arkhipov ◽  
Artem Malomouzh ◽  
Dmitry Samigullin
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Calcium Influx ◽  
Motor Nerve ◽  
Calcium Transient ◽  
Receptor Activation ◽  
Motor Nerve Terminal ◽  
Ach Release ◽  
Neuronal Nicotinic Receptors ◽  
Presynaptic Calcium

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse. ACh release was assessed by electrophysiological methods. Changes in calcium transients were recorded using a calcium-sensitive dye. Nicotine hydrogen tartrate salt application (10 μM) decreased the amount of evoked ACh release, while the calcium transient increased in the motor nerve terminal. Both of these effects of nicotine were abolished by the neuronal ACh receptor antagonist dihydro-beta-erythroidine and Cav1 blockers, verapamil, and nitrendipine. These data allow us to suggest that neuronal nicotinic ACh receptor activation decreases the number of ACh quanta released by boosting calcium influx through Cav1 channels.

Ca2+ signaling pathways linked to glutamate receptor activation in the somatic and dendritic regions of cultured cerebellar purkinje neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3325-3340 ◽  
Author(s):  
D. L. Gruol ◽  
J. G. Netzeband ◽  
K. L. Parsons
Keyword(s):  
Ryanodine Receptor ◽  
Glutamate Receptor ◽  
Time Course ◽  
Channel Blocker ◽  
Receptor Activation ◽  
Purkinje Neurons ◽  
Pharmacological Manipulation ◽  
P Type ◽  
Cerebellar Purkinje Neurons ◽  
Ca2 Channels

1. Ca2+ signaling elicited by ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (iGluR) and metabotropic (mGluR) glutamate receptor agonists was studied in the somatic and dendritic regions of cultured cerebellar Purkinje neurons using microscopic video imaging and the Ca2+ sensitive dye fura-2. 2. iGluR and mGluR agonists and K+ depolarization applied by brief micropressure pulses evoked Ca2+ signals in both the somatic and dendritic regions of all Purkinje neurons studied. The Ca2+ signals were generated simultaneously in both cellular regions. The Ca+ signals to these stimulants were similar in general form, consisting of an initial peak and slow recovery phase, but differed in details of amplitude, time course, and complexity. 3. Removal of extracellular Ca2+ abolished the Ca2+ signal to the iGluR agonist AMPA, indicating that Ca2+ influx was essential to the generation of Ca2+ signals by iGluR agonists. The Ca2+ channel blocker lanthanum almost completely eliminated the Ca2+ signals to AMPA, indicating that Ca2+ influx through voltage-sensitive Ca2+ channels was the main pathway for Ca2+ influx. Omega-agatoxin IVA, a P-type Ca2+ channel blocker, significantly reduced the Ca2+ signals to AMPA suggesting that Ca2+ influx was predominately through P-type Ca2+ channels. 4. Pharmacological manipulation of intracellular Ca2+ stores significantly reduced the Ca2+ signals to AMPA, indicating that release of Ca2+ from intracellular Ca2+ stores also plays a prominent role in the generation of the Ca2+ signals to iGluR agonists. These manipulations included blocking Ca2+ release from intracellular stores with dantrolene, an antagonist at the ryanodine receptor that controls Ca2+ release from one pool of intracellular Ca2+ stores, and depletion of intracellular Ca2+ stores with caffeine or ryanodine. 5. Ca2+ influx through voltage-sensitive Ca2+ channels did not appear to be involved in the Ca2+ signals to mGluR activation, because neither lanthanum nor omega-agatoxin IVA altered Ca2+ signals to mGluR agonists. Manipulation of intracellular stores with Ca(2+)-ATPase inhibitors and dantrolene significantly reduced the Ca2+ signal to mGluR agonists, indicating that Ca2+ signals were derived from both the inositol trisphosphate (IP3) and the ryanodine receptor-controlled intracellular Ca2+ stores. 6. Ca2+ signals to the iGluR agonist AMPA correlated temporally with the prolonged, multiphasic membrane responses elicited by similar agonist application in parallel electrophysiological studies. Pharmacological manipulation of Ca2+ influx and release of Ca2+ from intracellular stores significantly influenced components of the membrane response to AMPA, indicating a potential modulator or mediator role for Ca2+ in the membrane response to iGluR activation.

scholarly journals The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response

2003 ◽  
Vol 160 (4) ◽  
pp. 481-486 ◽  
Author(s):  
Emma-Jane Williams ◽  
Frank S. Walsh ◽  
Patrick Doherty
Keyword(s):  
Lipase Activity ◽  
Growth Response ◽  
Cannabinoid Receptor ◽  
Calcium Influx ◽  
Axonal Growth ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Neurotrophin Receptor ◽  
Fgf Receptor ◽  
Hydrolysis Of

Akey role for DAG lipase activity in the control of axonal growth and guidance in vitro and in vivo has been established. For example, DAG lipase activity is required for FGF-stimulated calcium influx into neuronal growth cones, and this response is both necessary and sufficient for an axonal growth response. The mechanism that couples the hydrolysis of DAG to the calcium response is not known. The initial hydrolysis of DAG at the sn-1 position (by DAG lipase) will generate 2-arachidonylglycerol, and this molecule is well established as an endogenous cannabinoid receptor agonist in the brain. In the present paper, we show that in rat cerebellar granule neurons, CB1 cannabinoid receptor antagonists inhibit axonal growth responses stimulated by N-cadherin and FGF2. Furthermore, three CB1 receptor agonists mimic the N-cadherin/FGF2 response at a step downstream from FGF receptor activation, but upstream from calcium influx into cells. In contrast, we could find no evidence for the CB1 receptor coupling the TrkB neurotrophin receptor to an axonal growth response in the same neurons. The observation that the CB1 receptor can couple the activated FGF receptor to an axonal growth response raises novel therapeutic opportunities.

Cocaine-induced increases in motivation require 2-arachidonoylglycerol mobilization and CB1 receptor activation in the ventral tegmental area

2021 ◽  
pp. 108625
Author(s):  
Sheila A. Engi ◽  
Erin J. Beebe ◽  
Victoria M. Ayvazian ◽  
Fabio C. Cruz ◽  
Joseph F. Cheer ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Ventral Tegmental
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