Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons

Yuliya V Medvedeva; Man-Su Kim; Yuriy M Usachev

doi:10.1523/JNEUROSCI.4810-07.2008

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Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons

Journal article

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Peer reviewed

Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons

Yuliya V Medvedeva, Man-Su Kim and Yuriy M Usachev

The Journal of neuroscience, Vol.28(20), pp.5295-5311

05/14/2008

DOI: 10.1523/JNEUROSCI.4810-07.2008

PMCID: PMC2694046

PMID: 18480286

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Abstract

Transient receptor potential vanilloid receptor 1 (TRPV1)-mediated release of neuroactive peptides and neurotransmitters from the peripheral and central terminals of primary sensory neurons can critically contribute to nociceptive processing at the periphery and in the CNS. However, the mechanisms that link TRPV1 activation with Ca2+ signaling at the release sites and neurosecretion are poorly understood. Here we demonstrate that a brief stimulation of the receptor using either capsaicin or the endogenous TRPV1 agonist N-arachidonoyl-dopamine induces a prolonged elevation of presynaptic [Ca2+](i) and a concomitant enhancement of glutamate release at sensory synapses. Initiation of this response required Ca2+ entry, primarily via TRPV1. The sustained phase of the response was independent of extracellular Ca2+ and was prevented by inhibitors of mitochondrial Ca2+ uptake and release mechanisms. Measurements using a mitochondria-targeted Ca2+ indicator, mtPericam, revealed that TRPV1 activation elicits a long-lasting Ca2+ elevation in presynaptic mitochondria. The concentration of TRPV1 agonist determined the duration of mitochondrial and cytosolic Ca2+ signals in presynaptic boutons and, consequently, the period of enhanced glutamate release and action potential firing by postsynaptic neurons. These data suggest that mitochondria control vanilloid-induced neurotransmission by translating the strength of presynaptic TRPV1 stimulation into duration of the postsynaptic response.

Posterior Horn Cells - drug effects

Posterior Horn Cells - metabolism

Synaptic Transmission - physiology

Calcium - metabolism

Capsaicin - pharmacology

Calcium Signaling - physiology

Coculture Techniques

Spinal Nerve Roots - metabolism

Pain - metabolism

TRPV Cation Channels - metabolism

Synaptic Transmission - drug effects

Afferent Pathways - drug effects

Action Potentials - drug effects

Afferent Pathways - metabolism

Animals, Newborn

Neurons, Afferent - drug effects

Presynaptic Terminals - drug effects

TRPV Cation Channels - agonists

Cells, Cultured

Dopamine - pharmacology

Rats

Mitochondria - metabolism

Mitochondria - drug effects

Rats, Sprague-Dawley

Arachidonic Acids - pharmacology

Action Potentials - physiology

Patch-Clamp Techniques

Animals

Dopamine - analogs & derivatives

Calcium Signaling - drug effects

Pain - physiopathology

Presynaptic Terminals - metabolism

Glutamic Acid - metabolism

Nociceptors - metabolism

Neurons, Afferent - metabolism

Ganglia, Spinal - drug effects

Nociceptors - drug effects

Spinal Nerve Roots - drug effects

Ganglia, Spinal - metabolism

Details

Title: Subtitle: Mechanisms of prolonged presynaptic Ca2+ signaling and glutamate release induced by TRPV1 activation in rat sensory neurons
Creators: Yuliya V Medvedeva - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Man-Su Kim
Yuriy M Usachev
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.28(20), pp.5295-5311
Publisher: United States
DOI: 10.1523/JNEUROSCI.4810-07.2008
PMID: 18480286
PMCID: PMC2694046
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01 NS054614-01A1 / NINDS NIH HHS R01 NS054614 / NINDS NIH HHS NS054614 / NINDS NIH HHS
Language: English
Date published: 05/14/2008
Academic Unit: Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984070578102771

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