Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles

evidence from the rat muscle spindle primary sensory ending

Guy S. Bewick, Brian Reid, Christine Richardson, Robert W. Banks

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Fifty-nanometre diameter, clear, synaptic-like vesicles (SLVs) are found in primary mechanosensory nerve terminals of vertebrate and invertebrate animals. We have investigated their role in mechanosensory function using the muscle spindle primary endings of rat Ia afferents as a model. Uptake and release of the synaptic vesicle marker FM1-43 indicated that SLVs recycle like synaptic vesicles and do so in a Ca2+-sensitive manner. Mechanical stimulation increased SLV recycling, increasing both dye uptake and release. Immunogold/electronmicroscopy showed that, like the central synaptic endings, la peripheral endings are enriched with glutamate. Moreover, exogenous glutamate enhanced stretch-induced la excitability. Enhanced excitability persisted in the presence of antagonists to the commonest ionotropic and metabotropic glutamate receptors (kynurenate, MCPG, CPPG and MAP4). However, excitation by glutamate was abolished by (R,S)-3,5-dihydroxyphenylglycine (DHPG), and rather more effectively by (2R,1'-S,2'-R,3'-S)-2-(2'-carboxy-3'-phenylcyclopropyl) glycine (PCCG-13). PCCG-13 also significantly reduced stretch-activated excitability in the absence of exogenous glutamate. These data indicate that SLVs recycle at rest, releasing glutamate, and that mechanical activity increases this process. The blockade with DHPG and PCCG-13 suggests that endogenous glutamate release acts, at least in part, through the recently described phospholipase D-linked metabotropic Glu receptor to maintain the excitability of the sensory endings.

Original languageEnglish
Pages (from-to)381-394
Number of pages13
JournalThe Journal of Physiology
Volume562
Issue number2
DOIs
Publication statusPublished - 15 Jan 2005

Keywords

  • peripheral nervous-system
  • inner hair-cells
  • cat spinal-cord
  • neuromuscular-junction
  • terminals
  • FM1-43
  • motor
  • afferents
  • mechanotransduction
  • immunoreactivity

Cite this

Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles : evidence from the rat muscle spindle primary sensory ending. / Bewick, Guy S. ; Reid, Brian; Richardson, Christine; Banks, Robert W. .

In: The Journal of Physiology, Vol. 562, No. 2, 15.01.2005, p. 381-394.

Research output: Contribution to journalArticle

@article{201b1ed9b82647bf817c718ae263ab36,
title = "Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles: evidence from the rat muscle spindle primary sensory ending",
abstract = "Fifty-nanometre diameter, clear, synaptic-like vesicles (SLVs) are found in primary mechanosensory nerve terminals of vertebrate and invertebrate animals. We have investigated their role in mechanosensory function using the muscle spindle primary endings of rat Ia afferents as a model. Uptake and release of the synaptic vesicle marker FM1-43 indicated that SLVs recycle like synaptic vesicles and do so in a Ca2+-sensitive manner. Mechanical stimulation increased SLV recycling, increasing both dye uptake and release. Immunogold/electronmicroscopy showed that, like the central synaptic endings, la peripheral endings are enriched with glutamate. Moreover, exogenous glutamate enhanced stretch-induced la excitability. Enhanced excitability persisted in the presence of antagonists to the commonest ionotropic and metabotropic glutamate receptors (kynurenate, MCPG, CPPG and MAP4). However, excitation by glutamate was abolished by (R,S)-3,5-dihydroxyphenylglycine (DHPG), and rather more effectively by (2R,1'-S,2'-R,3'-S)-2-(2'-carboxy-3'-phenylcyclopropyl) glycine (PCCG-13). PCCG-13 also significantly reduced stretch-activated excitability in the absence of exogenous glutamate. These data indicate that SLVs recycle at rest, releasing glutamate, and that mechanical activity increases this process. The blockade with DHPG and PCCG-13 suggests that endogenous glutamate release acts, at least in part, through the recently described phospholipase D-linked metabotropic Glu receptor to maintain the excitability of the sensory endings.",
keywords = "peripheral nervous-system, inner hair-cells, cat spinal-cord, neuromuscular-junction, terminals, FM1-43, motor, afferents, mechanotransduction, immunoreactivity",
author = "Bewick, {Guy S.} and Brian Reid and Christine Richardson and Banks, {Robert W.}",
year = "2005",
month = "1",
day = "15",
doi = "10.1113/JPHYSIOL.2004.074799",
language = "English",
volume = "562",
pages = "381--394",
journal = "The Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles

T2 - evidence from the rat muscle spindle primary sensory ending

AU - Bewick, Guy S.

AU - Reid, Brian

AU - Richardson, Christine

AU - Banks, Robert W.

PY - 2005/1/15

Y1 - 2005/1/15

N2 - Fifty-nanometre diameter, clear, synaptic-like vesicles (SLVs) are found in primary mechanosensory nerve terminals of vertebrate and invertebrate animals. We have investigated their role in mechanosensory function using the muscle spindle primary endings of rat Ia afferents as a model. Uptake and release of the synaptic vesicle marker FM1-43 indicated that SLVs recycle like synaptic vesicles and do so in a Ca2+-sensitive manner. Mechanical stimulation increased SLV recycling, increasing both dye uptake and release. Immunogold/electronmicroscopy showed that, like the central synaptic endings, la peripheral endings are enriched with glutamate. Moreover, exogenous glutamate enhanced stretch-induced la excitability. Enhanced excitability persisted in the presence of antagonists to the commonest ionotropic and metabotropic glutamate receptors (kynurenate, MCPG, CPPG and MAP4). However, excitation by glutamate was abolished by (R,S)-3,5-dihydroxyphenylglycine (DHPG), and rather more effectively by (2R,1'-S,2'-R,3'-S)-2-(2'-carboxy-3'-phenylcyclopropyl) glycine (PCCG-13). PCCG-13 also significantly reduced stretch-activated excitability in the absence of exogenous glutamate. These data indicate that SLVs recycle at rest, releasing glutamate, and that mechanical activity increases this process. The blockade with DHPG and PCCG-13 suggests that endogenous glutamate release acts, at least in part, through the recently described phospholipase D-linked metabotropic Glu receptor to maintain the excitability of the sensory endings.

AB - Fifty-nanometre diameter, clear, synaptic-like vesicles (SLVs) are found in primary mechanosensory nerve terminals of vertebrate and invertebrate animals. We have investigated their role in mechanosensory function using the muscle spindle primary endings of rat Ia afferents as a model. Uptake and release of the synaptic vesicle marker FM1-43 indicated that SLVs recycle like synaptic vesicles and do so in a Ca2+-sensitive manner. Mechanical stimulation increased SLV recycling, increasing both dye uptake and release. Immunogold/electronmicroscopy showed that, like the central synaptic endings, la peripheral endings are enriched with glutamate. Moreover, exogenous glutamate enhanced stretch-induced la excitability. Enhanced excitability persisted in the presence of antagonists to the commonest ionotropic and metabotropic glutamate receptors (kynurenate, MCPG, CPPG and MAP4). However, excitation by glutamate was abolished by (R,S)-3,5-dihydroxyphenylglycine (DHPG), and rather more effectively by (2R,1'-S,2'-R,3'-S)-2-(2'-carboxy-3'-phenylcyclopropyl) glycine (PCCG-13). PCCG-13 also significantly reduced stretch-activated excitability in the absence of exogenous glutamate. These data indicate that SLVs recycle at rest, releasing glutamate, and that mechanical activity increases this process. The blockade with DHPG and PCCG-13 suggests that endogenous glutamate release acts, at least in part, through the recently described phospholipase D-linked metabotropic Glu receptor to maintain the excitability of the sensory endings.

KW - peripheral nervous-system

KW - inner hair-cells

KW - cat spinal-cord

KW - neuromuscular-junction

KW - terminals

KW - FM1-43

KW - motor

KW - afferents

KW - mechanotransduction

KW - immunoreactivity

U2 - 10.1113/JPHYSIOL.2004.074799

DO - 10.1113/JPHYSIOL.2004.074799

M3 - Article

VL - 562

SP - 381

EP - 394

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 2

ER -