We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mechanisms of Prolonged Presynaptic Ca<sup>2+</sup> Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons.
- Authors
Medvedeva, Yuliya V.; Kim, Man-Su; Usachev, Yuriy M.
- 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.
- Subjects
SENSORY neurons; PRESYNAPTIC receptors; NEURAL transmission; NEUROTRANSMITTER receptors; NEUROTRANSMITTERS; GLUTAMIC acid; NEUROSCIENCES
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 20, p5295
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4810-07.2008