Effect of Propofol on Carotid Body Chemosensitivity and Cholinergic Chemotransduction

2005 ◽  
Vol 102 (1) ◽  
pp. 110-116 ◽  
Author(s):  
Malin M. Jonsson ◽  
Sten G. E. Lindahl ◽  
Lars I. Eriksson
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Carotid Body ◽  
Acetylcholine Receptors ◽  
Carotid Sinus ◽  
Aminobutyric Acid ◽  
Receptor Complex ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Carotid Sinus Nerve

Background Propofol decreases the acute hypoxic ventilatory response in humans and depresses in vivo carotid body chemosensitivity. The mechanisms behind this impaired oxygen sensing and signaling are not understood. Cholinergic transmission is involved in oxygen signaling, and because general anesthetics such as propofol have affinity to neuronal nicotinic acetylcholine receptors, the authors hypothesized that propofol depresses carotid body chemosensitivity and cholinergic signaling. Methods An isolated rabbit carotid body preparation was used. Chemoreceptor activity was recorded from the whole carotid sinus nerve. The effect of propofol on carotid body chemosensitivity was tested at three different degrees of PO2 reduction. Nicotine-induced chemoreceptor response was evaluated using bolus doses of nicotine given before and after propofol 10-500 microM. The contribution of the gamma-aminobutyric acid A receptor complex was tested by addition of gamma-aminobutyric acid A receptor antagonists. Results Propofol reduced carotid body chemosensitivity; the magnitude of depression was dependent on the reduction in PO2. Furthermore, propofol caused a concentration-dependent (10-500 microM) depression of nicotine-induced chemoreceptor response, with a 50% inhibitory concentration (propofol) of 40 microM. Bicuculline in combination with propofol did not have any additional effect, whereas addition of picrotoxin gave a slightly more pronounced inhibition. Conclusions It is concluded that propofol impairs carotid body chemosensitivity, the magnitude of depression being dependent on the severity of PO2 reduction, and that propofol causes a concentration-dependent block of cholinergic chemotransduction via the carotid sinus nerve, whereas it seems unlikely that an activation of the gamma-aminobutyric acid A receptor complex is involved in this interaction.

Halothane and Isoflurane Differentially Affect the Regulation of Dopamine and Gamma-aminobutyric Acid Release Mediated by Presynaptic Acetylcholine Receptors in the Rat Striatum

1997 ◽  
Vol 86 (3) ◽  
pp. 632-641 ◽  
Author(s):  
Francois Salord ◽  
Hawa Keita ◽  
Jean-Baptiste Lecharny ◽  
Danielle Henzel ◽  
Jean-Marie Desmonts ◽  
...  
Keyword(s):  
Potassium Chloride ◽  
Acetylcholine Receptors ◽  
Gaba Release ◽  
Volatile Anesthetics ◽  
Aminobutyric Acid ◽  
Rat Striatum ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Depolarizing Agents ◽  
Da Release

Background General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand-gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma-aminobutyric acid [GABA]) depolarization-evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum. Methods Assay for GABA (dopamine) release consisted of 3H-GABA (3H-DA)-preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5-5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10(-6)-10(-4) M) and/or atropine (10(-5) M) for experiments with 3H-GABA, and KC1 (15 mM) and nicotine (10(-7) - 5 x 10(-4) M) alone or with mecamylamine (10(-5) M) for experiments with 3H-DA. Results Potassium chloride induced a significant, Ca(2+)-dependent release of both 3H-GABA and 3H-DA. Nicotine produced a concentration-related, mecamylamine-sensitive 3H-DA release that was significantly attenuated by nicotine (10(-7) M) preincubation. Acetylcholine elicited a dose-dependent, atropine-sensitive reduction of the KC1-evoked 3H-GABA release. Halothane and isoflurane significantly decreased the nicotine-evoked 3H-DA release but had only limited depressant effects on the KC1-stimulated 3H-DA and no action on the KC1-induced 3H-GABA release. The effects of acetylcholine on 3H-GABA release were reversed by halothane but not by isoflurane. Conclusions Clinically relevant concentrations of halothane and isoflurane significantly, but differentially, alter the presynaptic cholinergic regulation of the release of inhibitory neurotransmitters in the striatum. These results suggest that the cholinergic transmission may represent an important and specific presynaptic target for volatile anesthetics in the CNS.

scholarly journals Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cathrine T. Fjordbakk ◽  
Jason A. Miranda ◽  
David Sokal ◽  
Matteo Donegà ◽  
Jaime Viscasillas ◽  
...  
Keyword(s):  
Carotid Body ◽  
Metabolic Diseases ◽  
Carotid Sinus ◽  
Alternating Current ◽  
Human Anatomy ◽  
Therapeutic Modality ◽  
Large Animal Model ◽  
Large Animal ◽  
Carotid Sinus Nerve

AbstractRecent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.

scholarly journals Murine Carotid Body Responses to Hypoxia: In vivo Carotid Sinus Nerve Recordings in the DBA/2J and A/J Strains.

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Luis Pichard ◽  
Francis Sgambati ◽  
Eric Kostuk ◽  
Pejmon Bashai ◽  
Robert Fitzgerald ◽  
...  
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Carotid Sinus Nerve ◽  
Nerve Recordings

N-cholinergic facilitation of glutamate release from an individual retinotectal fiber in frog

2001 ◽  
Vol 18 (4) ◽  
pp. 549-558 ◽  
Author(s):  
A. KURAS ◽  
N. GUTMANIENĖ
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Action Potentials ◽  
Acetylcholine Receptors ◽  
Kynurenic Acid ◽  
Glutamate Release ◽  
Synaptic Potentials ◽  
Lower Vertebrates ◽  
Optic Fibers ◽  
Retinotectal Transmission

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.

scholarly journals The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo

Neuron ◽  
2006 ◽  
Vol 51 (5) ◽  
pp. 587-600 ◽  
Author(s):  
Julie M. Miwa ◽  
Tanya R. Stevens ◽  
Sarah L. King ◽  
Barbara J. Caldarone ◽  
Ines Ibanez-Tallon ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine
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