Pioglitazone, a PPAR-γ activator, stimulates BK Ca but suppresses IK M in hippocampal neurons

Tsang Shan Chen, Ming Chi Lai, Te Yu Hung, Kao Min Lin, Chin-Wei Huang, Sheng-Nan Wu

研究成果: Article

5 引文 (Scopus)

摘要

Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ) with anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive activities. However, whether this compound exerts any perturbations on Ca 2+ -activated K + and M-type K + currents in central neurons remains largely unresolved. In this study, we investigated the effects of PIO on these potassium currents in hippocampal neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10 μM) increased the amplitude of Ca 2+ -activated K + current [IK(Ca)] in mHippoE-14 cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out current recordings, PIO applied to the bath concentration-dependently increased the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC50 value of 7.6 μM. Its activation of BK Ca channels in mHippoE-14 cells was voltage-dependent and accompanied by both a lengthening in mean open time and a shortening in slow component of mean closed time. The activation curve of BK Ca channels after addition of PIO was shifted to less depolarized potential without any change in the gating charge. PIO also suppressed the amplitude of M-type K + currents inherently in mHippoE-14 neurons. Taken together, in addition to its agonistic action on PPAR-γ, PIO-induced perturbation of these potassium channels may be responsible for its widely pharmacological actions on hippocampal neurons.

原文English
文章編號977
期刊Frontiers in Pharmacology
9
發行號AUG
DOIs
出版狀態Published - 2018 八月 29

指紋

pioglitazone
Peroxisome Proliferator-Activated Receptors
Neurons
Large-Conductance Calcium-Activated Potassium Channels
Apamin
Potassium Channels
Patch-Clamp Techniques
Baths

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

引用此文

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title = "Pioglitazone, a PPAR-γ activator, stimulates BK Ca but suppresses IK M in hippocampal neurons",
abstract = "Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ) with anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive activities. However, whether this compound exerts any perturbations on Ca 2+ -activated K + and M-type K + currents in central neurons remains largely unresolved. In this study, we investigated the effects of PIO on these potassium currents in hippocampal neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10 μM) increased the amplitude of Ca 2+ -activated K + current [IK(Ca)] in mHippoE-14 cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out current recordings, PIO applied to the bath concentration-dependently increased the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC50 value of 7.6 μM. Its activation of BK Ca channels in mHippoE-14 cells was voltage-dependent and accompanied by both a lengthening in mean open time and a shortening in slow component of mean closed time. The activation curve of BK Ca channels after addition of PIO was shifted to less depolarized potential without any change in the gating charge. PIO also suppressed the amplitude of M-type K + currents inherently in mHippoE-14 neurons. Taken together, in addition to its agonistic action on PPAR-γ, PIO-induced perturbation of these potassium channels may be responsible for its widely pharmacological actions on hippocampal neurons.",
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Pioglitazone, a PPAR-γ activator, stimulates BK Ca but suppresses IK M in hippocampal neurons . / Chen, Tsang Shan; Lai, Ming Chi; Hung, Te Yu; Lin, Kao Min; Huang, Chin-Wei; Wu, Sheng-Nan.

於: Frontiers in Pharmacology, 卷 9, 編號 AUG, 977, 29.08.2018.

研究成果: Article

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T1 - Pioglitazone, a PPAR-γ activator, stimulates BK Ca but suppresses IK M in hippocampal neurons

AU - Chen, Tsang Shan

AU - Lai, Ming Chi

AU - Hung, Te Yu

AU - Lin, Kao Min

AU - Huang, Chin-Wei

AU - Wu, Sheng-Nan

PY - 2018/8/29

Y1 - 2018/8/29

N2 - Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ) with anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive activities. However, whether this compound exerts any perturbations on Ca 2+ -activated K + and M-type K + currents in central neurons remains largely unresolved. In this study, we investigated the effects of PIO on these potassium currents in hippocampal neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10 μM) increased the amplitude of Ca 2+ -activated K + current [IK(Ca)] in mHippoE-14 cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out current recordings, PIO applied to the bath concentration-dependently increased the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC50 value of 7.6 μM. Its activation of BK Ca channels in mHippoE-14 cells was voltage-dependent and accompanied by both a lengthening in mean open time and a shortening in slow component of mean closed time. The activation curve of BK Ca channels after addition of PIO was shifted to less depolarized potential without any change in the gating charge. PIO also suppressed the amplitude of M-type K + currents inherently in mHippoE-14 neurons. Taken together, in addition to its agonistic action on PPAR-γ, PIO-induced perturbation of these potassium channels may be responsible for its widely pharmacological actions on hippocampal neurons.

AB - Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ) with anti-inflammatory, anti-proliferative, anti-diabetic, and antidepressive activities. However, whether this compound exerts any perturbations on Ca 2+ -activated K + and M-type K + currents in central neurons remains largely unresolved. In this study, we investigated the effects of PIO on these potassium currents in hippocampal neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10 μM) increased the amplitude of Ca 2+ -activated K + current [IK(Ca)] in mHippoE-14 cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out current recordings, PIO applied to the bath concentration-dependently increased the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels with an EC50 value of 7.6 μM. Its activation of BK Ca channels in mHippoE-14 cells was voltage-dependent and accompanied by both a lengthening in mean open time and a shortening in slow component of mean closed time. The activation curve of BK Ca channels after addition of PIO was shifted to less depolarized potential without any change in the gating charge. PIO also suppressed the amplitude of M-type K + currents inherently in mHippoE-14 neurons. Taken together, in addition to its agonistic action on PPAR-γ, PIO-induced perturbation of these potassium channels may be responsible for its widely pharmacological actions on hippocampal neurons.

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