title: Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells.
abstract: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+current [IK(DR)], were extensively investigated in differentiated NSC-34 neuronal cells.
  
  
  
  After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of IK(DR)followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of IK(DR)accompanied by increased gating charge of this current. However, the inactivation curve of IK(DR)remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of IK(DR)caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in IK(DR)activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+currents, although it effectively suppressed the amplitude of this current in untreated cells.
  
  
  
  The treatment of SGX may influence the amplitude and gating of IK(DR)and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City, 80708, Taiwan.|Department of Anesthesia, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, 80145, Taiwan.
authors.forename: Hung-Te
authors.initials: HT
authors.lastname: Hsu
authors.affiliation: Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung City, 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, No. 1, University Road, Tainan City, 70101, Taiwan.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung City, 80708, Taiwan.|Graduate Institute of Natural Products, School of Pharmacy, Kaohsiung Medical University, Kaohsiung City, 80708, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tseng
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, No. 1, University Road, Tainan City, 70101, Taiwan. snwu@mail.ncku.edu.tw.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D000077122:Sugammadex; D061566:Voltage-Gated Sodium Channels / Q000502:physiology; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
chemical_list: D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D005938:Glucocorticoids; D061566:Voltage-Gated Sodium Channels; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D003907:Dexamethasone
keywords: Activation kinetics; Delayed-rectifier K+ current; Glucocorticoid; L-type Ca2+ current; Motor neuron; Sugammadex