A gamma‐aminobutyric‐acid‐mediated inhibition of neurones in the nucleus tractus solitarius of the cat.

Bennett, JA; McWilliam, P. N.; Shepheard, Sara L.

doi:10.1113/jphysiol.1987.sp016788

Cited by 68 publications

(44 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is possible that glycine may not mimic the actions of L-AP4 due to simultaneous activation of inhibitory glycine receptors on chloride channels in the NTS (2,12,28). Thus, even if responses to L-AP4 are mediated by direct actions of L-AP4 at glycine-sensitive sites on NMDA channels, microinjection of glycine at L-AP4-sensitive sites in the NTS may or may not mimic the effects of L-AP4.…”

Section: Resultsmentioning

confidence: 97%

“…Urethane, glycine, and strychnine were obtained from Sigma Chemical (St. Louis, MO). Strychnine was used for its ability to prevent glycine activation of inhibitory chloride channels in the NTS (2,12,28) without affecting the potentiation of NMDA receptor-mediated responses by glycine (26,43). Thus by eliminating the inhibitory actions of glycine with strychnine, we would have expected to observe any excitatory actions of glycine in the NTS (decreases in MAP and SNA).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Mueller

Foley

Vogl

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Previous studies have demonstrated that microinjection of the putative group III metabotropic glutamate receptor (mGluR) agonist, L(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4), into the nucleus tractus solitarius (NTS) produces depressor and sympathoinhibitory responses. These responses are significantly attenuated by a group III mGluR antagonist and may involve ionotropic glutamatergic transmission. Alternatively, a previous report in vitro suggests that preparations of L-AP4 may nonspecifically activate NMDA channels due to glycine contamination (Contractor A, Gereau RW, Green T, and Heinemann SF. Proc Natl Acad Sci USA 95: 8969 -8974, 1998).Therefore, the present study tested whether responses to L-AP4 specifically require the N-methyl-D-aspartate (NMDA) receptor and whether they are due to actions at the glycine site on the NMDA channel. To test these possibilities in vivo, we performed unilateral microinjections of L-AP4, glycine, and selective antagonists into the NTS of urethane-anesthetized rats. L-AP4 (10 mM, 30 nl) produced sympathoinhibitory responses that were abolished by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP-5, 10 mM) but were unaffected by the non-NMDA antagonist 6-nitro-7-sulfamobenzoquinoxaline-2,3-dione (NBQX, 2 mM). Microinjection of glycine (0.02-20 mM) failed to mimic sympathoinhibitory responses to L-AP4, even in the presence of the inhibitory glycine antagonist, strychnine (3 mM). Strychnine blocked pressor and sympathoexcitatory actions of glycine (20 mM) but failed to reveal a sympathoinhibitory component due to presumed activation of NMDA receptors. The results of these experiments suggest that responses to L-AP4 require NMDA receptors and are independent of non-NMDA receptors. Furthermore, although it is possible that glycine contamination or other nonspecific actions are responsible for the sympathoinhibitory actions of L-AP4, our data and data in the literature argue against this possibility. Thus we conclude that responses to L-AP4 in the NTS are mediated by an interaction between group III mGluRs and NMDA receptors. Finally, we also caution that nonselective actions of L-AP4 should be considered in future studies.L-2-amino-4-phosphonobutyric acid; microinjection; metabotropic glutamate receptors; sympathetic nerve activity; nucleus tractus solitarius; N-methyl-O-aspartate THE NUCLEUS TRACTUS SOLITARIUS (NTS) is the primary termination site for baroreceptor afferents and is an important site for control of sympathetic outflow (47). Because glutamate appears to be the primary neurotransmitter of baroreceptor afferents (47, 50) and metabotropic glutamate receptors (mGluRs) are present in the NTS (4, 24, 25, 39), we and others have postulated that mGluRs may subserve various functions within the NTS (4,15,18,19,38). For example, group III mGluRs generally are believed to be presynaptic and inhibit neurotransmitter release in different brain regions (6,16,42), including the NTS (4, 20, 25). However, recent reports indicate that microinjection of group III recep...

show abstract

Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Mueller

Foley

Vogl

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…There is already electrophysiological evidence for tonic inhibitory mechanisms in both of these nuclei. In the nucleus tractus solitarius there is a tonic y-aminobutyric acid (GABA)-mediated inhibition of interneurones including interneurones receiving an input from aortic baroreceptors (Bennett, McWilliam & Shepheard, 1987). In the nucleus ambiguus both GABA and acetylcholine have tonic inhibitory actions, with acetylcholine mediating the inspiratory-related inhibition of cardiac vagal motoneurones (Spyer & Jordan, 1987).…”

Section: Discussionmentioning

confidence: 99%

Changes in the baroreceptor reflex at the start of muscle contraction in the decerebrate cat.

McWilliam

Yang

Chen

1991

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

SUMMARY1. The action of muscle contraction on the sensitivity of the cardiac vagal component of the baroreceptor reflex was examined in decerebrate cats.2. The sensitivity of the baroreceptor reflex was expressed as the difference between the maximum prolongation of the R-R interval in response to carotid sinus baroreceptor stimulation and the mean of ten R-R intervals immediately before carotid sinus pressure elevation.3. Muscle contraction elicited by electrical stimulation of L7 ventral roots (50 Hz) significantly reduced the sensitivity of the baroreceptor reflex by reducing the prolongation of the R-R interval from 269 + 31 to 159 + 22 ms.4. Inhibition of the cardiac vagal component of the baroreceptor reflex was seen just 1 s after the onset of contraction and with stimulation frequencies as low as 10 Hz.5. These results show for the first time that changes in the sensitivity of the baroreceptor reflex during exercise result in part from afferent information originating in the contracting muscles.

show abstract

“…Indeed, a unique possibility might include actions of propofol on GABA A receptors containing ρ 1 subunits which are expressed in NTS (Milligan et al, 2004). In intact animals, ongoing activity of GABA pathways was suggested by observations that GABA antagonists increased spontaneous firing (Bennett et al, 1987). The molecular basis of tonic GABA A currents is controversial.…”

Section: Propofol Induces a Tonic Inhibitory Currentmentioning

confidence: 99%

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

et al. 2008

View full text Add to dashboard Cite

The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter" <200 µs), "all-or-none" glutamatergic excitatory postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol prolonged miniature IPSC decay time constants by 50% above control at 1.8 µM. Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher concentrations, propofol (30 µM) induced a gabazine-insensitive tonic current that was blocked by picrotoxin or bicuculline. In contrast, total propofol concentrations up to 30 µM had no effect on EPSCs. Thus, propofol enhanced phasic GABA events in NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.

show abstract

A gamma‐aminobutyric‐acid‐mediated inhibition of neurones in the nucleus tractus solitarius of the cat.

Cited by 68 publications

References 24 publications

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Changes in the baroreceptor reflex at the start of muscle contraction in the decerebrate cat.

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

Contact Info

Product

Resources

About