摘要
Naringenin (NGEN) is a citrus bioflavonoid known to have beneficial health properties; however, the ionic mechanism of its actions remains largely unclear. In this study, we attempted to evaluate the possible effects of NGEN on K+ currents in NSC-34 neuronal cells and in HEK293T cells expressing α-hSlo. Results: NGEN increased M-type K+ current (IK(M)) in a concentration-dependent manner with an EC50 value of 9.8 μM in NSC-34 cells. NGEN shifted the activation curve of IK(M) conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K+ (KM) channels with no changes in single-channel amplitude. NGEN (10 μM) had minimal effect on erg-mediated K+ currents. Under cell-attached voltage-clamp recordings, NGEN decreased the frequency of spontaneous action currents and further application of linopirdine can reverse NGEN-induced inhibition of firing. In HEK293T cells expressing α-hSlo, this compound increased the amplitude of Ca2+-activated K+ current (IK(Ca)). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Moreover, from the study of a modeled neuron, burst firing of simulated action potentials (APs) was reduced in the presence of the increased conductances of both KM and KCa channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both KM and BKCa channels were increased by two-fold, the voltage nullcline was shifted in an upward direction accompanied by the compression of burst trajectory. Conclusions: The present results demonstrate that activation of both KM and BKCa channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.
| 原文 | English |
|---|---|
| 文章編號 | 135 |
| 期刊 | BMC Neuroscience |
| 卷 | 15 |
| 發行號 | 1 |
| DOIs | |
| 出版狀態 | Published - 2014 十二月 24 |
指紋
All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Cellular and Molecular Neuroscience
引用此文
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Ability of naringenin, a bioflavonoid, to activate M-type potassium current in motor neuron-like cells and to increase BKCa-channel activity in HEK293T cells transfected with α-hSlo subunit. / Hsu, Hung Te; Tseng, Yu Ting; Lo, Yi Ching; Wu, Sheng-Nan.
於: BMC Neuroscience, 卷 15, 編號 1, 135, 24.12.2014.研究成果: Article
TY - JOUR
T1 - Ability of naringenin, a bioflavonoid, to activate M-type potassium current in motor neuron-like cells and to increase BKCa-channel activity in HEK293T cells transfected with α-hSlo subunit
AU - Hsu, Hung Te
AU - Tseng, Yu Ting
AU - Lo, Yi Ching
AU - Wu, Sheng-Nan
PY - 2014/12/24
Y1 - 2014/12/24
N2 - Naringenin (NGEN) is a citrus bioflavonoid known to have beneficial health properties; however, the ionic mechanism of its actions remains largely unclear. In this study, we attempted to evaluate the possible effects of NGEN on K+ currents in NSC-34 neuronal cells and in HEK293T cells expressing α-hSlo. Results: NGEN increased M-type K+ current (IK(M)) in a concentration-dependent manner with an EC50 value of 9.8 μM in NSC-34 cells. NGEN shifted the activation curve of IK(M) conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K+ (KM) channels with no changes in single-channel amplitude. NGEN (10 μM) had minimal effect on erg-mediated K+ currents. Under cell-attached voltage-clamp recordings, NGEN decreased the frequency of spontaneous action currents and further application of linopirdine can reverse NGEN-induced inhibition of firing. In HEK293T cells expressing α-hSlo, this compound increased the amplitude of Ca2+-activated K+ current (IK(Ca)). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Moreover, from the study of a modeled neuron, burst firing of simulated action potentials (APs) was reduced in the presence of the increased conductances of both KM and KCa channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both KM and BKCa channels were increased by two-fold, the voltage nullcline was shifted in an upward direction accompanied by the compression of burst trajectory. Conclusions: The present results demonstrate that activation of both KM and BKCa channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.
AB - Naringenin (NGEN) is a citrus bioflavonoid known to have beneficial health properties; however, the ionic mechanism of its actions remains largely unclear. In this study, we attempted to evaluate the possible effects of NGEN on K+ currents in NSC-34 neuronal cells and in HEK293T cells expressing α-hSlo. Results: NGEN increased M-type K+ current (IK(M)) in a concentration-dependent manner with an EC50 value of 9.8 μM in NSC-34 cells. NGEN shifted the activation curve of IK(M) conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K+ (KM) channels with no changes in single-channel amplitude. NGEN (10 μM) had minimal effect on erg-mediated K+ currents. Under cell-attached voltage-clamp recordings, NGEN decreased the frequency of spontaneous action currents and further application of linopirdine can reverse NGEN-induced inhibition of firing. In HEK293T cells expressing α-hSlo, this compound increased the amplitude of Ca2+-activated K+ current (IK(Ca)). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Moreover, from the study of a modeled neuron, burst firing of simulated action potentials (APs) was reduced in the presence of the increased conductances of both KM and KCa channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both KM and BKCa channels were increased by two-fold, the voltage nullcline was shifted in an upward direction accompanied by the compression of burst trajectory. Conclusions: The present results demonstrate that activation of both KM and BKCa channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.
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UR - http://www.scopus.com/inward/citedby.url?scp=84924035835&partnerID=8YFLogxK
U2 - 10.1186/s12868-014-0135-1
DO - 10.1186/s12868-014-0135-1
M3 - Article
C2 - 25539574
AN - SCOPUS:84924035835
VL - 15
JO - BMC Neuroscience
JF - BMC Neuroscience
SN - 1471-2202
IS - 1
M1 - 135
ER -