title: 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.
abstract: BACKGROUND
  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 (I(K(M))) in a concentration-dependent manner with an EC50 value of 9.8 μM in NSC-34 cells. NGEN shifted the activation curve of I(K(M)) conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K(+) (K(M)) 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 Ca(2+)-activated K(+) current (I(K(Ca))). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca(2+)-activated K(+) (BK(Ca)) 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 K(M) and K(Ca) channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both K(M) and BK(Ca) 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 K(M) and BK(Ca) channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. hdhsu1228@hotmail.com.|Department of Anesthesia, Kaohsiung Medical University Hospital, Kaohsiung City, 80708, Taiwan. hdhsu1228@hotmail.com.
authors.forename: Hung-Te
authors.initials: HT
authors.lastname: Hsu
authors.affiliation: Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. mmship1112@yahoo.com.tw.|Graduate Institute of Natural Products, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. mmship1112@yahoo.com.tw.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. yichlo@kmu.edu.tw.|Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. yichlo@kmu.edu.tw.|Graduate Institute of Natural Products, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. yichlo@kmu.edu.tw.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, Tainan City, 70101, Taiwan. snwu@mail.ncku.edu.tw.|Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City, 70101, Taiwan. snwu@mail.ncku.edu.tw.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014162:Transfection
chemical_list: D000631:Aminopyridines; D044950:Flavanones; D007211:Indoles; C494841:KCNMA1 protein, human; D051656:KCNQ Potassium Channels; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D011725:Pyridines; C005273:naringenin; C061017:linopirdine; C034161:flupirtine; D011188:Potassium