The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice

Jacobson, Gregory M.; Voss, Logan J.; Melin, Sofia M.; Cursons, Raymond T.; Sleigh, James W.

doi:10.1111/j.1365-2044.2011.06658.x

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…The fluranes, however, are all ethers and are expected to have different mechanisms of action. One mechanism of action of isoflurane and sevoflurane is the modulation of gap junction mediated signaling . It is also reported that different length perfluorinated compounds can inhibit gap junction intercellular communication .…”

Section: Discussionmentioning

confidence: 99%

Feasibility and Safety of Contrast‐enhanced Ultrasound in the Distal Limb of Six Horses

Seiler

Campbell

Nixon

et al. 2016

Vet Radiology Ultrasound

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Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases.

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Section: Discussionmentioning

confidence: 99%

Feasibility and Safety of Contrast‐enhanced Ultrasound in the Distal Limb of Six Horses

Seiler

Campbell

Nixon

et al. 2016

Vet Radiology Ultrasound

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show abstract

“…This theory, underpinned by the “Meyer‐Overton correlation”, held for about 80 years, until it was refuted in the late 80s by elegant experiments indicating that the targets must involve proteins pockets because general anesthetics are stereospecific . Since then, every molecular mechanism seems to have been proposed for general anesthesia, from nonspecific effects on various proteins to specific channel targets to gap junctions and microtubules . Accordingly, general anesthetics appear to impair the function of a wide range of molecules, as determined by in vitro assays , although it is now generally accepted that GABA A receptors represent a major target for most of these drugs .…”

Section: Sleep and Synaptic Mechanisms Together May Explain General Amentioning

confidence: 99%

Explaining general anesthesia: A two‐step hypothesis linking sleep circuits and the synaptic release machinery

Swinderen

Kottler

2014

BioEssays

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Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two-step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non-sleeping systems can be made insensitive (or hypersensitive) to some anesthetics by modifying a single pre-synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep.

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“…Thus the knockout experiments, together with a subset of the pharmacological experiments, suggest that interneuronal gap junctions may be protective against seizure, and that their ablation can enhance pathological excitability. There are also data that suggest that Cx36 knockout mice are more sensitive to the hypnotic effects of anesthetic drugs (Jacobson et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex

Steyn-Ross

Sleigh

2012

Cogn Neurodyn

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During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (≲8 Hz) oscillatory states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity for seizure and simultaneously an increased sensitivity to GABAergic anesthesia.

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The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice

Cited by 12 publications

References 36 publications

Feasibility and Safety of Contrast‐enhanced Ultrasound in the Distal Limb of Six Horses

Feasibility and Safety of Contrast‐enhanced Ultrasound in the Distal Limb of Six Horses

Explaining general anesthesia: A two‐step hypothesis linking sleep circuits and the synaptic release machinery

Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex

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