Modulation of hyperpolarization-activated cation current Ih by volatile anesthetic sevoflurane in the mouse striatum during postnatal development

Sugasawa, Yusuke; Fukuda, Masataka; Ando, Nozomi; Inoue, Ritsuko; Nakauchi, Sakura; Miura, Masami; Nishimura, Kinya

doi:10.1016/j.neures.2017.09.009

Cited by 3 publications

(5 citation statements)

References 41 publications

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“…Instead, sevoflurane substantially reduced the I h current amplitude in a dose-dependent manner. In line with previous findings, the observed effects of sevoflurane on HCN channel function suggest a complex inhibitory modulation instead of a channel block (Sugasawa et al, 2018). This constitutes a notable difference compared to other anesthetic agents like propofol (Ying et al, 2006).…”

Section: Discussionsupporting

confidence: 89%

“…Further, halothane leads to a slowing of current activation in the case of HCN2 with an opposite effect for HCN1 (Chen et al, 2005). Comparable to our results, a marked divergence between a reduction of I h current amplitude and a rather modest shift in the voltage dependence of I h activation was also observed in hypoglossal motoneurons in the presence of halothane (Sirois et al, 1998) and in cholinergic interneurons of the striatum in the presence of sevoflurane (Sugasawa et al, 2018). In the latter case, these neurons mainly express HCN2 and HCN4 subunits as well (Santoro et al, 2000).…”

Section: Discussionsupporting

confidence: 76%

“…Consistent with our findings, sevoflurane dose-dependently reduced maximal I h current amplitude, whereas 4.0 vol.% sevoflurane (recordings performed at 30 • C) only induced a modest shift in the half-activation potential towards hyperpolarization (−4.1 mV). The authors of this study therefore hypothesized that sevoflurane acts as an HCN channel modulator rather than a channel blocker (Sugasawa et al, 2018). Correspondingly, we found that coapplication of the selective HCN channel blocker ZD7288 (0.04 mM) with sevoflurane resulted in a markedly stronger reduction of I h maximal current amplitude as well as an additional hyperpolarization of the resting membrane potential.…”

Section: Discussionsupporting

confidence: 52%

“…However, its effect on native HCN channel function in thalamocortical relay neurons remains poorly understood. Available electrophysiological data are either exploratory in nature (Budde et al, 2008) or stem from different neuronal cell populations (Sirois et al, 1998;Sugasawa et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons

Schwerin

Kopp

Pircher

et al. 2021

Front. Cell. Neurosci.

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As thalamocortical relay neurons are ascribed a crucial role in signal propagation and information processing, they have attracted considerable attention as potential targets for anesthetic modulation. In this study, we analyzed the effects of different concentrations of sevoflurane on the excitability of thalamocortical relay neurons and hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels, which play a decisive role in regulating membrane properties and rhythmic oscillatory activity. The effects of sevoflurane on single-cell excitability and native HCN channels were investigated in acutely prepared brain slices from adult wild-type mice with the whole-cell patch-clamp technique, using voltage-clamp and current-clamp protocols. Sevoflurane dose-dependently depressed membrane biophysics and HCN-mediated parameters of neuronal excitability. Respective half-maximal inhibitory and effective concentrations ranged between 0.30 (95% CI, 0.18–0.50) mM and 0.88 (95% CI, 0.40–2.20) mM. We witnessed a pronounced reduction of HCN dependent Ih current amplitude starting at a concentration of 0.45 mM [relative change at −133 mV; 0.45 mM sevoflurane: 0.85 (interquartile range, 0.79–0.92), n = 12, p = 0.011; 1.47 mM sevoflurane: 0.37 (interquartile range, 0.34–0.62), n = 5, p < 0.001] with a half-maximal inhibitory concentration of 0.88 (95% CI, 0.40–2.20) mM. In contrast, effects on voltage-dependent channel gating were modest with significant changes only occurring at 1.47 mM [absolute change of half-maximal activation potential; 1.47 mM: −7.2 (interquartile range, −10.3 to −5.8) mV, n = 5, p = 0.020]. In this study, we demonstrate that sevoflurane inhibits the excitability of thalamocortical relay neurons in a concentration-dependent manner within a clinically relevant range. Especially concerning its effects on native HCN channel function, our findings indicate substance-specific differences in comparison to other anesthetic agents. Considering the importance of HCN channels, the observed effects might mechanistically contribute to the hypnotic properties of sevoflurane.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons

Schwerin

Kopp

Pircher

et al. 2021

Front. Cell. Neurosci.

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“…The striatal medium spiny (MS) neurons were identified according to their morphology using an infrared differential interference contrast video microscope (BX50WI; Olympus, Tokyo, Japan) and their characteristic firing patterns in response to depolarizing and hyperpolarizing step currents. After recordings, the slice was immunostained for biocytin to confirm a recording site (Ando et al., ; Sugasawa et al., ). Measurements were not corrected for liquid junction potentials of 10 mV.…”

Section: Methodsmentioning

confidence: 99%

Volatile anesthetic sevoflurane pretreatment alleviates hypoxia‐induced potentiation of excitatory inputs to striatal medium spiny neurons of mice

Fukuda

Ando

Sugasawa

et al. 2019

Eur J of Neuroscience

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Sevoflurane, a commonly used anesthetic in surgery, has drawn attention because of its preconditioning effects in hypoxic conditions. To investigate the preconditioning effects in the striatum, a common site for ischemic stroke, we collected whole‐cell current‐clamp recordings from striatal medium spiny neurons. In our in vitro brain slice experiments, deprivation of oxygen and glucose depolarized the striatal neurons to subthreshold potentials, and the pre‐administration of sevoflurane (4%, 15 min) prolonged the time to depolarization. Furthermore, transient hypoxia induced the potentiation of excitatory postsynaptic potentials, which play a part in post‐ischemic excitotoxicity. Glibenclamide, a KATP channel inhibitor, reversed the prolonged time to depolarization and the prevention of the pathological potentiation of excitatory responses, indicating that the short exposure to sevoflurane likely participates in neuroprotection against hypoxia via activation of KATP channels. A monocarboxylate transporter blocker, 4‐CIN, also depolarized striatal neurons. Interestingly, the blockade of monocarboxylate transporters that supply lactate to neurons caused the pathological potentiation, even in the presence of enough oxygen and glucose. In this case, sevoflurane could not prevent the pathological potentiation, suggesting the involvement of monocarboxylate transporters in the sevoflurane‐mediated effects. These results indicate that sevoflurane protects striatal neurons from hypoxic damage and alleviates the pathological potentiation. Under these conditions, sevoflurane may become an effective intervention for patients undergoing surgery.

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Sevoflurane excites nociceptive sensory neurons by inhibiting K+ conductances in rats

Lee

Nakamura

Cho

et al. 2021

Neuroscience Letters

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Modulation of hyperpolarization-activated cation current Ih by volatile anesthetic sevoflurane in the mouse striatum during postnatal development

Cited by 3 publications

References 41 publications

Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons

Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons

Volatile anesthetic sevoflurane pretreatment alleviates hypoxia‐induced potentiation of excitatory inputs to striatal medium spiny neurons of mice

Sevoflurane excites nociceptive sensory neurons by inhibiting K+ conductances in rats

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