Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals

Liu, Qing-Zhuo; Mei, Hao; Zhou, Zhiqiang; Ge, Jian-long; Wu, Yanxin; Zhao, Lei; Wu, Xiang; Feng, Yi; Gao, Hong Zhi; Li, Shun; Xue, Lei

doi:10.1007/s13238-019-0624-1

Cited by 13 publications

(15 citation statements)

References 12 publications

(12 reference statements)

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“…The PPR at baseline was 0.77 ± 0.13 and increased to 1.13 ± 0.15 after BDNF application ( p = 0.0006, repeated-measures one-way ANOVA with Bonferroni post hoc test; n = 8; Fig. 1 A , bottom, B ), suggesting a presynaptic mechanism for BDNF-inhibited synaptic transmission ( Liu et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Sprague Dawley rats of either sex were used on postnatal day 8-10 (p8-p10). Brain slices were prepared as described previously ( Sun et al, 2016 ; Liu et al, 2019 ). Briefly, after the pups were decapitated, and blocks of tissue containing the medial nucleus of the trapezoid body (MNTB) were quickly immersed in low calcium ACSF solution, pH 7.4, containing the following (in m m ): 125 NaCl, 25 NaHCO 3 , 3 myo -inositol, 2.5 KCl, 1.25 NaH 2 PO 4 , 2 sodium pyruvate, 3 MgCl 2 , 0.05 CaCl 2 , 0.4 ascorbic acid, and 25 glucose.…”

Section: Methodsmentioning

confidence: 99%

“…For paired-pulse recording, a paired stimulus was applied with an interval of 20 ms to induce two consecutive EPSCs. The paired-pulse ratio (PPR) was calculated as the second EPSC divided by the first EPSC (Liu et al, 2019).…”

Section: Animals Slice Preparation and Electrophysiologymentioning

confidence: 99%

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BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse

Liu

Guo

et al. 2020

J. Neurosci.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse

Liu

Guo

et al. 2020

J. Neurosci.

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“…In addition, propofol regulates the intrinsic membrane properties by modulating the extra-synaptic GABA receptor 43 . On the other hand, propofol inhibits presynaptic sodium channels, resulting in the reduction of glutamatergic synaptic transmission 44 , normalizes the increased expression of glutamate in the hippocampus of rats with sleep deprivation 45 , and inhibits the veratridine-evoked glutamate release in the synaptosomes from rat brain regions 46 . Finally, propofol can reverse the oxygen-glucose deprivation-induced elevation of the extracellular glutamate concentrations by reducing glutamate uptake 47 , and inhibits glutamatergic activation by acting on protein kinases 24 .…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice

Yang

Ton

Zhao

et al. 2020

Sci Rep

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Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.

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“…With the discovery of other targets, such as AMPA receptors, sodium channels, potassium channels, and calcium channels (Zhu et al, 1997;Ouyang et al, 2003;Liu et al, 2019), it has become apparent that general anesthetics affect multiple specific receptors (Franks and Lieb, 1984). Voltage-gated sodium channels (Na V ) are the main channels which conduct the Na + current inwardly, controlling the initiation and propagation of action potentials in nerves, muscles, and neuroendocrine cells.…”

Section: Introductionmentioning

confidence: 99%

A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol

Xiao

Chen

2020

Front. Cell. Neurosci.

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General anesthesia has revolutionized healthcare over the past 200 years and continues to show advancements. However, many phenomena induced by general anesthetics including paradoxical excitation are still poorly understood. Voltage-gated sodium channels (NaV) were believed to be one of the proteins targeted during general anesthesia. Based on electrophysiological measurements before and after propofol treatments of different concentrations, we mathematically modified the Hodgkin–Huxley sodium channel formulations and constructed a thalamocortical model to investigate the potential roles of NaV. The ion channels of individual neurons were modeled using the Hodgkin–Huxley type equations. The enhancement of propofol-induced GABAa current was simulated by increasing the maximal conductance and the time-constant of decay. Electroencephalogram (EEG) was evaluated as the post-synaptic potential from pyramidal (PY) cells. We found that a left shift in activation of NaV was induced primarily by a low concentration of propofol (0.3–10 μM), while a left shift in inactivation of NaV was induced by an increasing concentration (0.3–30 μM). Mathematical simulation indicated that a left shift of NaV activation produced a Hopf bifurcation, leading to cell oscillations. Left shift of NaV activation around a value of 5.5 mV in the thalamocortical models suppressed normal bursting of thalamocortical (TC) cells by triggering its chaotic oscillations. This led to irregular spiking of PY cells and an increased frequency in EEG readings. This observation suggests a mechanism leading to paradoxical excitation during general anesthesia. While a left shift in inactivation led to light hyperpolarization in individual cells, it inhibited the activity of the thalamocortical model after a certain depth of anesthesia. This finding implies that high doses of propofol inhibit the network partly by accelerating NaV toward inactivation. Additionally, this result explains why the application of sodium channel blockers decreases the requirement for general anesthetics. Our study provides an insight into the roles that NaV plays in the mechanism of general anesthesia. Since the activation and inactivation of NaV are structurally independent, it should be possible to avoid side effects by state-dependent binding to the NaV to achieve precision medicine in the future.

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Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals

Cited by 13 publications

References 12 publications

BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse

BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse

Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice

A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol

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