Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons

Chin-Wei Huang, Kao Min Lin, Te Yu Hung, Yao Chung Chuang, Sheng-Nan Wu

研究成果: Article

3 引文 (Scopus)

摘要

Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of I Na with an IC 50 value of 39.3 μM; however, neither activation nor inactivation kinetics of I Na was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of I Na . Rot increased the amplitude of Ca 2+ -activated Cl - current in response to membrane depolarization with an EC 50 value of 35.4 μM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 μM Rot, a specific population of ATP-sensitive K + channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 μM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

原文English
頁(從 - 到)330-343
頁數14
期刊Cellular Physiology and Biochemistry
47
發行號1
DOIs
出版狀態Published - 2018 六月 1

指紋

Miniature Postsynaptic Potentials
Rotenone
Electron Transport
Neurons
Niflumic Acid
Ions
Membranes
Vulnerable Populations
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Physiology

引用此文

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title = "Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons",
abstract = "Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of I Na with an IC 50 value of 39.3 μM; however, neither activation nor inactivation kinetics of I Na was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of I Na . Rot increased the amplitude of Ca 2+ -activated Cl - current in response to membrane depolarization with an EC 50 value of 35.4 μM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 μM Rot, a specific population of ATP-sensitive K + channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 μM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.",
author = "Chin-Wei Huang and Lin, {Kao Min} and Hung, {Te Yu} and Chuang, {Yao Chung} and Sheng-Nan Wu",
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T1 - Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons

AU - Huang, Chin-Wei

AU - Lin, Kao Min

AU - Hung, Te Yu

AU - Chuang, Yao Chung

AU - Wu, Sheng-Nan

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of I Na with an IC 50 value of 39.3 μM; however, neither activation nor inactivation kinetics of I Na was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of I Na . Rot increased the amplitude of Ca 2+ -activated Cl - current in response to membrane depolarization with an EC 50 value of 35.4 μM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 μM Rot, a specific population of ATP-sensitive K + channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 μM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

AB - Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of I Na with an IC 50 value of 39.3 μM; however, neither activation nor inactivation kinetics of I Na was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of I Na . Rot increased the amplitude of Ca 2+ -activated Cl - current in response to membrane depolarization with an EC 50 value of 35.4 μM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 μM Rot, a specific population of ATP-sensitive K + channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 μM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

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