Howells James, Bostock Hugh, Burke David
Brain & Mind Centre, The University of Sydney, Sydney, Australia;
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom; and.
J Neurophysiol. 2016 Aug 1;116(2):322-35. doi: 10.1152/jn.00019.2016. Epub 2016 Apr 20.
Human axons in vivo were subjected to subthreshold currents with a threshold impedance amplitude profile to allow the use of frequency domain techniques to determine the propensity for resonant behavior and to clarify the relative contributions of different ion channels to their low-frequency responsiveness. Twenty-four studies were performed on the motor and sensory axons of the median nerve in six subjects. The response to oscillatory currents was tested between direct current (DC) and 16 Hz. A resonant peak at ∼2-2.5 Hz was found in the response of hyperpolarized axons, but there was only a small broad response in axons at resting membrane potential (RMP). A mathematical model of axonal excitability developed using DC pulses provided a good fit to the frequency response for human axons and indicated that the hyperpolarization-activated current Ih and the slow potassium current IKs are principally responsible for the resonance. However, the results indicate that if axons are hyperpolarized by more than -60% of resting threshold, the only conductances that are appreciably active are Ih and the leak conductance, i.e., that the activity of these conductances can be studied in vivo virtually in isolation at hyperpolarized membrane potentials. Given that the leak conductance dampens resonance, it is suggested that the -60% hyperpolarization used here is optimal for Ih As expected, differences between the frequency responses of motor and sensory axons were present and best explained by reduced slow potassium conductance GKs, up-modulation of Ih, and increased persistent Na(+) current INaP (due to depolarization of RMP) in sensory axons.
在体内，对人类轴突施加具有阈值阻抗幅度分布的阈下电流，以便使用频域技术来确定共振行为的倾向，并阐明不同离子通道对其低频反应性的相对贡献。对6名受试者正中神经的运动和感觉轴突进行了24项研究。测试了在直流（DC）和16 Hz之间对振荡电流的反应。在超极化轴突的反应中发现了一个约2 - 2.5 Hz的共振峰，但静息膜电位（RMP）下的轴突只有一个小的宽反应。使用直流脉冲建立的轴突兴奋性数学模型与人类轴突的频率反应拟合良好，并表明超极化激活电流Ih和慢钾电流IKs是共振的主要原因。然而，结果表明，如果轴突超极化超过静息阈值的-60%，唯一明显活跃的电导是Ih和漏电导，即这些电导的活性实际上可以在超极化膜电位下在体内单独研究。鉴于漏电导会抑制共振，建议此处使用的-60%超极化对Ih是最佳的。正如预期的那样，运动和感觉轴突的频率反应存在差异，最好的解释是感觉轴突中慢钾电导GK降低、Ih上调以及持续性钠电流INaP增加（由于RMP去极化）。
