Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

Lin, Ming‐Wei; Wang, Ya-Jean; Liu, Shiuh–Inn; Lin, Anan; Lo, Yi-Ching; Wu, Sheng‐Nan

doi:10.1016/j.neuropharm.2008.01.009

Cited by 31 publications

(33 citation statements)

References 33 publications

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“…Importantly, our study demonstrated that the activation kinetics of I K(DR) (i.e., K V 3.1-encoded current) in SGX-treated cells virtually became slowed in a time- and state-dependent manner. The results were in contrast with inhibitory effects of midazolam or aconitine on I K(DR) [12, 21]. These two compounds exerted inhibitory effects via a mechanism through binding to the open state of the channel followed by increased rate of I K(DR) inactivation.…”

Section: Discussionmentioning

confidence: 89%

“…Current amplitudes were increased with greater depolarizations in an outward-rectifying manner with a reversal potential of −76 ± 2 mV (n = 12). These outward currents, which were insensitive to inhibition by either iberiotoxin (200 nM) or apamin (200 nM), have been referred to as I K(DR) , the biophysical properties of which resemble the K V 3.1-encoded K + currents [12, 22]. In particular, as the cells were exposed to SGX (30 μM), the amplitude and gating of I K(DR) were altered throughout the entire range of voltage-clamp steps as compared with those taken from untreated cells.…”

Section: Resultsmentioning

confidence: 99%

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Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Hsu

Huang

et al. 2017

BMC Neurosci

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BackgroundSugammadex (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.ResultsAfter cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I 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 of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I 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 of I 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 in I 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.ConclusionsThe treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-016-0320-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Hsu

Huang

et al. 2017

BMC Neurosci

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“…The pipettes used had a resistance of 3–5 MΩ when immersed in different solutions as described above. Patch-clamp recordings were made in cell-attached or whole-cell configurations using an RK-400 (Bio-Logic, Claix, France) or an Axopatch 200B patch-clamp amplifier (Molecular Devices; Sunnyvale, CA, USA) [15, 16]. …”

Section: Methodsmentioning

confidence: 99%

Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K⁺Currents in Motor Neuron-Like Cells

Hsu

Liao

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Flupirtine (Flu), a triaminopyridine derivative, is a centrally acting, non-opiate analgesic agent. In this study, effects of Flu on K+ currents were explored in two types of motor neuron-like cells. Cell exposure to Flu decreased the amplitude of delayed rectifier K+ current (I K(DR)) with a concomitant raise in current inactivation in NSC-34 neuronal cells. The dissociation constant for Flu-mediated increase of I K(DR) inactivation rate was about 9.8 μM. Neither linopirdine (10 μM), NMDA (30 μM), nor gabazine (10 μM) reversed Flu-induced changes in I K(DR) inactivation. Addition of Flu shifted the inactivation curve of I K(DR) to a hyperpolarized potential. Cumulative inactivation for I K(DR) was elevated in the presence of this compound. Flu increased the amplitude of M-type K+ current (I K(M)) and produced a leftward shift in the activation curve of I K(M). In another neuronal cells (NG108-15), Flu reduced I K(DR) amplitude and enhanced the inactivation rate of I K(DR). The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K+ channels in motor neurons. Flu-induced block of I K(DR) is unlinked to binding to NMDA or GABA receptors and the effects of this agent on K+ channels are not limited to its action on M-type K+ channels.

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“…In this study, the inhibitory effect of ART on I K(DR) observed in GH 3 cells can be taken into account by a state-dependent blocker that binds to the open state of K V channels according to a minimal kinetic scheme [18]. The blocking and unblocking rate constants (i.e., k +1 and k -1 ) were appropriately determined from the inactivation rate constants (i.e., 1/τ inact ) of I K(DR) elicited by the voltage steps from -50 to +50 mV with a duration of 10 sec.…”

Section: Kinetic Study Of Art Effect On I K(dr)mentioning

confidence: 99%

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

Wu³

et al. 2017

Cell Physiol Biochem

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Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH₃) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K⁺ current (I_K(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I_K(DR) with an IC₅₀ value of 11.2 µM and enhanced I_K(DR) inactivation with a K_D value of 14.7 µM. The steady-state inactivation curve of I_K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I_K(DR) in GH₃ cells. ART also decreased the peak amplitude of voltage-gated Na⁺ current (I_Na) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I_Na, was effective at reversing ART-induced prolongation in inactivation time constant of I_Na. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I_K(DR) and I_Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

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Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

Cited by 31 publications

References 33 publications

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K⁺Currents in Motor Neuron-Like Cells

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

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Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

Cited by 31 publications

References 33 publications

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells

Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K+Currents in Motor Neuron-Like Cells

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

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Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K⁺Currents in Motor Neuron-Like Cells