The origin of hyperpolarization based on the directional conduction of action potential using a model nerve cell system

Kaji, Maiko; Kitazumi, Yuki; Kano, Kenji; Shirai, Osamu

doi:10.1016/j.bioelechem.2019.03.007

Cited by 7 publications

(9 citation statements)

References 25 publications

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“…Membrane hyperpolarization was not produced by the operation of delayed-rectifier K + currents and voltage-gated Na + currents. However, from a model nerve cell system, a recent report showed the presence of hyperpolarization-mediated change in the conduction during action potential firing [57], suggesting that either I h , I MEP or both in response to membrane hyperpolarization might have the propensity to perturb the conduction along the axon during electrical firing. In this study we were unable to observe suppressive effect of OXAL (3 µM) on proliferating GH 3 cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Chang

Gao

et al. 2020

IJMS

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Oxaliplatin (OXAL) is regarded as a platinum-based anti-neoplastic agent. However, its perturbations on membrane ionic currents in neurons and neuroendocrine or endocrine cells are largely unclear, though peripheral neuropathy has been noted during its long-term administration. In this study, we investigated how the presence of OXAL and other related compounds can interact with two types of inward currents; namely, hyperpolarization-activated cation current (Ih) and membrane electroporation-induced current (IMEP). OXAL increased the amplitude or activation rate constant of Ih in a concentration-dependent manner with effective EC50 or KD values of 3.2 or 6.4 μM, respectively, in pituitary GH3 cells. The stimulation by this agent of Ih could be attenuated by subsequent addition of ivabradine, protopine, or dexmedetomidine. Cell exposure to OXAL (3 μM) resulted in an approximately 11 mV rightward shift in Ih activation along the voltage axis with minimal changes in the gating charge of the curve. The exposure to OXAL also effected an elevation in area of the voltage-dependent hysteresis elicited by long-lasting triangular ramp. Additionally, its application resulted in an increase in the amplitude of IMEP elicited by large hyperpolarization in GH3 cells with an EC50 value of 1.3 μM. However, in the continued presence of OXAL, further addition of ivabradine, protopine, or dexmedetomidine always resulted in failure to attenuate the OXAL-induced increase of IMEP amplitude effectively. Averaged current-voltage relation of membrane electroporation-induced current (IMEP) was altered in the presence of OXAL. In pituitary R1220 cells, OXAL-stimulated Ih remained effective. In Rolf B1.T olfactory sensory neurons, this agent was also observed to increase IMEP in a concentration-dependent manner. In light of the findings from this study, OXAL-mediated increases of Ih and IMEP may coincide and then synergistically act to increase the amplitude of inward currents, raising the membrane excitability of electrically excitable cells, if similar in vivo findings occur.

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Section: Discussionmentioning

confidence: 99%

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Chang

Gao

et al. 2020

IJMS

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“…A liquid‐membrane cell comprises two aqueous phases (W1 and W2) and a nitrobenzene phase (NB), as described in Figure SI‐1 [23, 24]. The NB solution was impregnated in a porous polytetrafluoroethylene membrane filter T100A025A (pore size: 1 μm, thickness: 75 μm, ADVANTEC TOYO KAISHA, Ltd., Japan), and the filter was used as a liquid membrane (LM).…”

Section: Methodsmentioning

confidence: 99%

“…The authors’ group has elucidated the propagation of the change in the membrane potential using a nerve‐model‐cell system with multiple liquid‐membrane cells [16–24]. Several liquid‐membrane cells were connected using a switch, multiple relay switches, and multiple timers within the electric circuit to mimic a function of K + and Na + channels [20, 21].…”

Section: Introductionmentioning

confidence: 99%

“…Several liquid‐membrane cells were connected using a switch, multiple relay switches, and multiple timers within the electric circuit to mimic a function of K + and Na + channels [20, 21]. It was shown that the change in the membrane potential from the resting potential to the action potential was caused by the external electric stimulus and that the directional propagation of the action potential could be reproduced using the model system [22, 23].…”

Section: Introductionmentioning

confidence: 99%

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Severe Problems of the Voltage‐Clamp Method in Concurrent Monitoring of Membrane Potentials

et al. 2022

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In nerve cells, the concurrent monitoring of multipoint on the axon has been conducted based on the voltage‐clamp method using two long parallel electrodes inside and outside the axon. As the respective membrane potentials have been evaluated by considering the clamping potential, the local current, and the conductance, the membrane potentials were not actually evaluated. We directly measured the actual membrane potentials and local currents of the respective cells using a nerve‐model‐system comprising some liquid‐membrane cells. It is proved that the action potential propagation is artificially facilitated or prevented by both the external electric generator and two long electrodes.

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“…In neurons, the fire rate, pattern, directionality, and threshold of action potentials are determined by the location, distribution, kinetics, and expression level of Na v and K v channels [98,113,250]. Ultimately, the ensemble of functionally active Na v and K v channels in axons, dendrites, and somas will determine the likelihood of forward vs. backpropagation of action potentials, which, in turn, affects synaptic transmission at presynaptic axonal terminals (forward propagation) and synaptic input integration (backward propagation) in the dendritic tree [251][252][253].…”

Section: Potential Mechanisms By Which Gsk3β Influences Neuronal Exci...mentioning

confidence: 99%

Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases

Marosi

Arman

Aceto

et al. 2022

IJMS

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Glycogen synthase kinase 3β (GSK3) is a multifaceted serine/threonine (S/T) kinase expressed in all eukaryotic cells. GSK3β is highly enriched in neurons in the central nervous system where it acts as a central hub for intracellular signaling downstream of receptors critical for neuronal function. Unlike other kinases, GSK3β is constitutively active, and its modulation mainly involves inhibition via upstream regulatory pathways rather than increased activation. Through an intricate converging signaling system, a fine-tuned balance of active and inactive GSK3β acts as a central point for the phosphorylation of numerous primed and unprimed substrates. Although the full range of molecular targets is still unknown, recent results show that voltage-gated ion channels are among the downstream targets of GSK3β. Here, we discuss the direct and indirect mechanisms by which GSK3β phosphorylates voltage-gated Na+ channels (Nav1.2 and Nav1.6) and voltage-gated K+ channels (Kv4 and Kv7) and their physiological effects on intrinsic excitability, neuronal plasticity, and behavior. We also present evidence for how unbalanced GSK3β activity can lead to maladaptive plasticity that ultimately renders neuronal circuitry more vulnerable, increasing the risk for developing neuropsychiatric disorders. In conclusion, GSK3β-dependent modulation of voltage-gated ion channels may serve as an important pharmacological target for neurotherapeutic development.

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The origin of hyperpolarization based on the directional conduction of action potential using a model nerve cell system

Cited by 7 publications

References 25 publications

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Severe Problems of the Voltage‐Clamp Method in Concurrent Monitoring of Membrane Potentials

Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases

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