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

Hung Te Hsu, Yu Ting Tseng, Yi Ching Lo, Sheng Nan Wu

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

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
15
發行號1
DOIs
出版狀態Published - 2014 十二月 24

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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