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A modeling study predicts the presence of voltage gated Ca(2+) channels on myelinated central axons.

机译:一项模型研究预测,髓鞘中央轴突上存在电压门控Ca(2+)通道。

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摘要

The objective of this current study was to investigate whether voltage gated Ca(2+) channels are present on axons of the adult rat optic nerve (RON). Simulations of axonal excitability using a Hodgkin-Huxley based one-compartment model incorporating I(Na), I(K) and leak currents were used to predict conditions under which the potential contribution of a Ca(2+) current to an evoked action potential could be measured. Under control conditions the inclusion of a high threshold Ca(2+) current (I(Ca)) in the model had a negligible effect on the action potential. Reducing I(K), by decreasing the value of g(K), elongated the repolarizing phase of the action potential, increasing its duration. Subsequent incorporation of I(Ca) in the model revealed a significant I(Ca) contribution to the repolarizing phase of the action potential. The simulation thus suggests that Ca(2+) channels may be present on RON axons, but that pharmacological intervention is required to unmask their presence. Experiments based on the simulations revealed that there was no significant contribution of I(Ca) to the control action potential. However, as predicted by the simulation, reducing the repolarizing effect of I(K) by adding the K(+) channel blocker 4-AP revealed a Ca(2+) component on the repolarizing phase of the action potential that was blocked by the Ca(2+) channel inhibitor nifedipine.
机译:这项当前研究的目的是调查成年大鼠视神经(RON)的轴突上是否存在电压门控Ca(2+)通道。使用结合I(Na),I(K)和泄漏电流的基于Hodgkin-Huxley的单室模型模拟轴突兴奋性,以预测条件下Ca(2+)电流对诱发动作电位的潜在作用可以测量。在控制条件下,模型中包含高阈值Ca(2+)电流(I(Ca))对动作电位的影响可忽略不计。通过减小g(K)的值来减小I(K),可以延长动作电位的复极化阶段,从而增加其持续时间。随后在模型中加入I(Ca)揭示了I(Ca)对动作电位复极化阶段的重要作用。因此,模拟表明RON轴突上可能存在Ca(2+)通道,但是需要药理干预才能掩盖它们的存在。基于模拟的实验表明,I(Ca)对控制动作电位没有显着贡献。但是,如模拟所预测的,通过添加K(+)通道阻滞剂4-AP降低I(K)的复极化作用,揭示了Ca(2+)成分对被电势阻断的动作电位的复极化阶段。 Ca(2+)通道抑制剂硝苯地平。

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