Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Hung Te Hsu, Yi Ching Lo, Yan Ming Huang, Yu Ting Tseng, Sheng-Nan Wu

研究成果: Article

3 引文 (Scopus)

摘要

Background: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+ current [I K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. Results: After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I K(DR) followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of I K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in I K(DR) activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+ currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. Conclusions: The treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.

原文English
文章編號6
期刊BMC Neuroscience
18
發行號1
DOIs
出版狀態Published - 2017 一月 3

指紋

Cyclodextrins
Ions
Sugammadex
Neuromuscular Blocking Agents
Membranes
Motor Neurons
General Anesthesia
Dexamethasone
Glucocorticoids
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

引用此文

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title = "Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells",
abstract = "Background: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+ current [I K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. Results: After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I K(DR) followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of I K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in I K(DR) activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+ currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. Conclusions: The treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.",
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Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells. / Hsu, Hung Te; Lo, Yi Ching; Huang, Yan Ming; Tseng, Yu Ting; Wu, Sheng-Nan.

於: BMC Neuroscience, 卷 18, 編號 1, 6, 03.01.2017.

研究成果: Article

TY - JOUR

T1 - Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

AU - Hsu, Hung Te

AU - Lo, Yi Ching

AU - Huang, Yan Ming

AU - Tseng, Yu Ting

AU - Wu, Sheng-Nan

PY - 2017/1/3

Y1 - 2017/1/3

N2 - Background: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+ current [I K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. Results: After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I K(DR) followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of I K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in I K(DR) activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+ currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. Conclusions: The treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.

AB - Background: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+ current [I K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. Results: After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I K(DR) followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of I K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in I K(DR) activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+ currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. Conclusions: The treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.

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