Modulation of afferent excitability and reflex responses by phospholipase D-coupled metabotropic glutamate receptors in the peripheral terminals of rat arterial baroreceptors

Julian Paton, Robert Banks, Guy Smith Bewick

Research output: Contribution to journalAbstract

Abstract

Vertebrate primary mechanosensory nerve terminals contain populations of clear synaptic-like vesicles (SLVs). We have demonstrated glutamate released from SLVs produces autogenic modulation of mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles and guard hair follicles (Bewick et al., 2005; Singh et al., 2009), acting on phospholipase D-linked metabotropic glutamate receptors (PLD-mGluRs). Our aim here was to test whether the SLVs in baroreceptor endings (Krauhs, 1979) indicate a similar mechanism can modulate afferent discharge and reflex-evoked responses. Male Wistar rats (60-100g) were prepared for the working heart-brainstem preparation (Paton, 1996) by deeply anaesthetising with halothane (by inhalation) until loss of paw and tail withdrawal reflex then bisected sub-diaphragmatically. The animals were decerebrated at the precollicular level to ensure insentience before anaesthesia was discontinued. Perfusion pressure (PP), heart rate (HR) and thoracic chain sympathetic nerve activity (SNA) were recorded. Baroreceptors were stimulated by ramp increases in PP while either afferent discharge or reflex changes in HR and SNA were measured after superfusion of the aortic arch with either the PLD-mGluR antagonist PCCG-13 (20 μM) or glutamate (10 mM). Afferent activity data were normalised as μV/mmHg and expressed as % change and the gain of the cardiac baroreceptor reflex response expressed as beats/min(bpm)/mmHg. Data are from 4 rats and expressed as mean ± SEM; statistical significance was determined using a Student’s t-test. PCCG-13 decreased baroreceptor activity by 35.4 ± 5.0% (P<0.05) whereas glutamate increased discharge by 42.0 ± 6.0% (P<0.05) relative to control levels; both effects were reversible. Control cardiac baroreceptor reflex gain was 2.8 ± 0.4 bpm/mmHg but was attenuated reversibly following application of PCCG-13 (-50.7%; P<0.05). The baroreceptor reflex-mediated sympathoinhibition was also depressed (n = 1). Finally, glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals can effectively regulate afferent activity through PLD-mGluRs, to modulate reflex cardiac and sympathomotor responses. Together with similar systems in hair follicle and muscle spindle afferent terminals, this is consistent with a general role for SLVs in glutamatergic modulation of peripheral mechanosensory terminals.
Original languageEnglish
Article numberC79
JournalProceedings of the Physiological Society
Volume19
Publication statusPublished - 2010
EventPhysiology 2010 - Manchester, United Kingdom
Duration: 30 Jun 20102 Jul 2010

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Phospholipase D
Pressoreceptors
Metabotropic Glutamate Receptors
Baroreflex
Synaptic Vesicles
Reflex
Glutamic Acid
Muscle Spindles
Hair Follicle
Thoracic Aorta
Perfusion
Heart Rate
Pressure
Architectural Accessibility
Mechanoreceptors
Halothane
Inhalation
Brain Stem
Vertebrates
Tail

Cite this

@article{afe3c25e76c645fcad10ab199a2b0674,
title = "Modulation of afferent excitability and reflex responses by phospholipase D-coupled metabotropic glutamate receptors in the peripheral terminals of rat arterial baroreceptors",
abstract = "Vertebrate primary mechanosensory nerve terminals contain populations of clear synaptic-like vesicles (SLVs). We have demonstrated glutamate released from SLVs produces autogenic modulation of mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles and guard hair follicles (Bewick et al., 2005; Singh et al., 2009), acting on phospholipase D-linked metabotropic glutamate receptors (PLD-mGluRs). Our aim here was to test whether the SLVs in baroreceptor endings (Krauhs, 1979) indicate a similar mechanism can modulate afferent discharge and reflex-evoked responses. Male Wistar rats (60-100g) were prepared for the working heart-brainstem preparation (Paton, 1996) by deeply anaesthetising with halothane (by inhalation) until loss of paw and tail withdrawal reflex then bisected sub-diaphragmatically. The animals were decerebrated at the precollicular level to ensure insentience before anaesthesia was discontinued. Perfusion pressure (PP), heart rate (HR) and thoracic chain sympathetic nerve activity (SNA) were recorded. Baroreceptors were stimulated by ramp increases in PP while either afferent discharge or reflex changes in HR and SNA were measured after superfusion of the aortic arch with either the PLD-mGluR antagonist PCCG-13 (20 μM) or glutamate (10 mM). Afferent activity data were normalised as μV/mmHg and expressed as {\%} change and the gain of the cardiac baroreceptor reflex response expressed as beats/min(bpm)/mmHg. Data are from 4 rats and expressed as mean ± SEM; statistical significance was determined using a Student’s t-test. PCCG-13 decreased baroreceptor activity by 35.4 ± 5.0{\%} (P<0.05) whereas glutamate increased discharge by 42.0 ± 6.0{\%} (P<0.05) relative to control levels; both effects were reversible. Control cardiac baroreceptor reflex gain was 2.8 ± 0.4 bpm/mmHg but was attenuated reversibly following application of PCCG-13 (-50.7{\%}; P<0.05). The baroreceptor reflex-mediated sympathoinhibition was also depressed (n = 1). Finally, glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals can effectively regulate afferent activity through PLD-mGluRs, to modulate reflex cardiac and sympathomotor responses. Together with similar systems in hair follicle and muscle spindle afferent terminals, this is consistent with a general role for SLVs in glutamatergic modulation of peripheral mechanosensory terminals.",
author = "Julian Paton and Robert Banks and Bewick, {Guy Smith}",
year = "2010",
language = "English",
volume = "19",
journal = "Proceedings of the Physiological Society",
issn = "1749-6187",

}

TY - JOUR

T1 - Modulation of afferent excitability and reflex responses by phospholipase D-coupled metabotropic glutamate receptors in the peripheral terminals of rat arterial baroreceptors

AU - Paton, Julian

AU - Banks, Robert

AU - Bewick, Guy Smith

PY - 2010

Y1 - 2010

N2 - Vertebrate primary mechanosensory nerve terminals contain populations of clear synaptic-like vesicles (SLVs). We have demonstrated glutamate released from SLVs produces autogenic modulation of mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles and guard hair follicles (Bewick et al., 2005; Singh et al., 2009), acting on phospholipase D-linked metabotropic glutamate receptors (PLD-mGluRs). Our aim here was to test whether the SLVs in baroreceptor endings (Krauhs, 1979) indicate a similar mechanism can modulate afferent discharge and reflex-evoked responses. Male Wistar rats (60-100g) were prepared for the working heart-brainstem preparation (Paton, 1996) by deeply anaesthetising with halothane (by inhalation) until loss of paw and tail withdrawal reflex then bisected sub-diaphragmatically. The animals were decerebrated at the precollicular level to ensure insentience before anaesthesia was discontinued. Perfusion pressure (PP), heart rate (HR) and thoracic chain sympathetic nerve activity (SNA) were recorded. Baroreceptors were stimulated by ramp increases in PP while either afferent discharge or reflex changes in HR and SNA were measured after superfusion of the aortic arch with either the PLD-mGluR antagonist PCCG-13 (20 μM) or glutamate (10 mM). Afferent activity data were normalised as μV/mmHg and expressed as % change and the gain of the cardiac baroreceptor reflex response expressed as beats/min(bpm)/mmHg. Data are from 4 rats and expressed as mean ± SEM; statistical significance was determined using a Student’s t-test. PCCG-13 decreased baroreceptor activity by 35.4 ± 5.0% (P<0.05) whereas glutamate increased discharge by 42.0 ± 6.0% (P<0.05) relative to control levels; both effects were reversible. Control cardiac baroreceptor reflex gain was 2.8 ± 0.4 bpm/mmHg but was attenuated reversibly following application of PCCG-13 (-50.7%; P<0.05). The baroreceptor reflex-mediated sympathoinhibition was also depressed (n = 1). Finally, glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals can effectively regulate afferent activity through PLD-mGluRs, to modulate reflex cardiac and sympathomotor responses. Together with similar systems in hair follicle and muscle spindle afferent terminals, this is consistent with a general role for SLVs in glutamatergic modulation of peripheral mechanosensory terminals.

AB - Vertebrate primary mechanosensory nerve terminals contain populations of clear synaptic-like vesicles (SLVs). We have demonstrated glutamate released from SLVs produces autogenic modulation of mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles and guard hair follicles (Bewick et al., 2005; Singh et al., 2009), acting on phospholipase D-linked metabotropic glutamate receptors (PLD-mGluRs). Our aim here was to test whether the SLVs in baroreceptor endings (Krauhs, 1979) indicate a similar mechanism can modulate afferent discharge and reflex-evoked responses. Male Wistar rats (60-100g) were prepared for the working heart-brainstem preparation (Paton, 1996) by deeply anaesthetising with halothane (by inhalation) until loss of paw and tail withdrawal reflex then bisected sub-diaphragmatically. The animals were decerebrated at the precollicular level to ensure insentience before anaesthesia was discontinued. Perfusion pressure (PP), heart rate (HR) and thoracic chain sympathetic nerve activity (SNA) were recorded. Baroreceptors were stimulated by ramp increases in PP while either afferent discharge or reflex changes in HR and SNA were measured after superfusion of the aortic arch with either the PLD-mGluR antagonist PCCG-13 (20 μM) or glutamate (10 mM). Afferent activity data were normalised as μV/mmHg and expressed as % change and the gain of the cardiac baroreceptor reflex response expressed as beats/min(bpm)/mmHg. Data are from 4 rats and expressed as mean ± SEM; statistical significance was determined using a Student’s t-test. PCCG-13 decreased baroreceptor activity by 35.4 ± 5.0% (P<0.05) whereas glutamate increased discharge by 42.0 ± 6.0% (P<0.05) relative to control levels; both effects were reversible. Control cardiac baroreceptor reflex gain was 2.8 ± 0.4 bpm/mmHg but was attenuated reversibly following application of PCCG-13 (-50.7%; P<0.05). The baroreceptor reflex-mediated sympathoinhibition was also depressed (n = 1). Finally, glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals can effectively regulate afferent activity through PLD-mGluRs, to modulate reflex cardiac and sympathomotor responses. Together with similar systems in hair follicle and muscle spindle afferent terminals, this is consistent with a general role for SLVs in glutamatergic modulation of peripheral mechanosensory terminals.

M3 - Abstract

VL - 19

JO - Proceedings of the Physiological Society

JF - Proceedings of the Physiological Society

SN - 1749-6187

M1 - C79

ER -