Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Hsu, Hung-Te; Lo, Yi-Ching; Huang, Yan-Ming; Tseng, Yu-Ting; Wu, Sheng-Nan
• Is Part Of: BMC neuroscience. Volume 18:Issue 1(2017)
• Page Start: 1
• Page End: 12
• Publication Date: 2017-12
• Subjects: Sugammadex -- Motor neuron -- Delayed-rectifier K+ current -- Activation kinetics -- L-type Ca2+ current -- Glucocorticoid; Neurosciences -- Periodicals; 573.805
• DOI: 10.1186/s12868-016-0320-5
• Languages: English
• ISSNs: 1471-2202

Abstract

Abstract Background 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 [I K(DR) ], were extensively investigated in differentiated NSC-34 neuronal cells. Results After cells were exposed to SGX (30 μM), there was a reduction in the amplitude ofI K(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 ofI K(DR) accompanied by increased gating charge of this current. However, the inactivation curve ofI K(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 ofI K(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 inI K(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. Conclusions The treatment of SGX may influence the amplitude and gating ofI K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.