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

Abstract

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.

Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells

“…In addition, gambierol slowed the kinetics of K + current activation in fetal AMC cells, implying a delayed opening of the K V channels upon membrane depolarization (Figure 4C). In agreement with previous reports of such an effect [17,43,44], this strongly suggests that the polyether has a greater affinity for the channel resting state [45]. This particularity distinguishes the gambierol action from that of other lipophilic polyether toxins, such as Pacific ciguatoxin-1 (P-CTX-1) which also blocks K V channels in rat myotubes and sensory neurons [46,47].…”

Effective Perturbations by Phenobarbital on INa, IK(erg), IK(M) and IK(DR) during Pulse Train Stimulation in Neuroblastoma Neuro-2a Cells

“…In this study, we found that the I K(DR) in Neuro-2a cells can be susceptible to being blocked by PHB, and the cumulative inhibition of I K(DR) during prolonged (i.e., 10 s) repetitive stimulation was enhanced ( Figure 9 ). Consequently, the magnitude of I Na recovery from current inactivation during PT stimulation would become slowed owing to the enhanced cumulative inhibition of I K(erg) , I K(DR) , and I K(M) [ 27 , 31 , 57 ]. In this scenario, as cells were exposed to PHB, the high-frequency firing of neuronal APs would lose the emergence of APs’ stable waveforms leading to serious perturbations in high-fidelity synaptic signaling (e.g., the presynaptic release of neurotransmitters) [ 56 ].…”

Dexamethasone Treatment Increases the Intracellular Calcium Level Through TRPV6 in A549 Cells

“…In addition, TRPV or NCX1 gene expressions by RU486 could be partly and indirectly attributed to its suppression in calcium currents. Acute treatment with DEX or mifepristone (RU486) might suppress calcium channels in electrically excitable cells, such as motor neurons and vascular smooth muscle cells (VSMCs) [25,26]. Therefore, a DEX-mediated change in intracellular calcium level may be discernable in electrically excitable cells such as tracheal smooth muscle cells.…”