Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat.
Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat.
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DOI：
10.1111/j.1440-1681.2010.05396.x
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发表时间：
2010-08
影响因子：
2.9
通讯作者：
Schild JH
中科院分区：
文献类型：
--
作者：
Zhou YH;Sun LH;Liu ZH;Bu G;Pang XP;Sun SC;Qiao GF;Li BY;Schild JH
超极化诱导的阳离子选择性电流，Ih，被广泛观察到在迷走神经和背根神经节的外周感觉神经元，但峰值幅度以及电压和时间依赖性的特性，这种电流的传入纤维类型之间的差异很大。通过膜片钳研究确定为有髓鞘的A型传入神经元的离体大鼠迷走神经节神经元，我们建立了一个简编的功能相关的膜电位的变化和这些感觉神经元的动态放电特性的结果，Ih的控制招聘使用电流钳技术。响应超极化阶跃电流的两个稳健观察结果：1）在负阶跃电流开始时，由于Ih的稳态募集，膜电位出现快速超极化，随后出现去极化下降（DVS），朝向膜电位的平台，和2）当负阶跃电流终止时，有一个快速恢复到测试前的静息膜电位，这通常导致自发动作电位放电这些数据与这些A型VGN的动态放电特征的广泛纲要密切相关（r2 > 0.9）。在响应去极化阶跃电流的增加幅度的放电频率的A型VGN总结可靠地响应持续重复放电的速率增加。在去极化阶跃电流终止时，存在兴奋性后膜超极化，其幅度与动作电位放电速率强烈相关（r2 > 0.9）。应用选择性HCN通道阻断剂10 µM ZD 7288或1.0 mM CsCl，除了降低A型VGN对阶跃去极化电流的兴奋性外，还消除了Ih和所有上述功能相关性。随着越来越多的证据表明HCN通道电流可能代表药理学干预的有效靶点，这种定量关系可能有助于指导HCN通道门控特性的分子或化学修饰，以影响VGN放电特性的特定结果。理想情况下，远远超出了对特定HCN通道亚型的选择性阻断。
The hyperpolarization induced cation selective current, Ih, is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia but the peak magnitude as well as the voltage and time dependent properties of this current vary widely across afferent fiber type. Through patch clamp study of isolated rat vagal ganglion neurons identified as myelinated A-type afferents we establish a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of Ih using the current clamp technique. Two robust observations in response to hyperpolarizing step currents: 1) upon initiation of the negative step current there was a rapid hyperpolarization of membrane potential followed by a depolarizing sag (DVS) toward a plateau in membrane potential as a result of steady state recruitment of Ih, and 2) upon termination of the negative step current there was a rapid return to the pretest resting membrane potential that often led to spontaneous action potential discharge. These data strongly correlated (r2 > 0.9) with a broad compendium of dynamic discharge characteristics in these A-type VGN. In response to depolarizing step currents of increasing magnitude the discharge frequency of the A-type VGN summarize reliably responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current there was a post excitatory membrane hyperpolarization with a magnitude that strongly correlated with action potential discharge rate (r2 > 0.9). Application of the selective HCN channel blockers 10 µM ZD7288 or 1.0 mM CsCl abolished Ih and all of the aforementioned functional correlates in addition to reducing the excitability of the A-type VGN to step depolarizing currents. As evidence is growing that the HCN channel current may represent a valid target for pharmacological intervention such quantitative relationships could potentially help guide the molecular or chemical modification of HCN channel gating properties to effect a particular outcome in VGN discharge properties. Ideally, well beyond merely selective blockade of a particular HCN channel subtype.
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DOI：
10.1085/jgp.200709868
发表时间：
2008-03
期刊：
The Journal of general physiology
影响因子：
--
作者：
Lyashchenko AK;Tibbs GR
通讯作者：
Tibbs GR
DOI：
10.1152/physiologyonline.2002.17.1.32
发表时间：
2002-02-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Accili, EA;Proenza, C;DiFrancesco, D
通讯作者：
DiFrancesco, D
影响因子：
5.1
作者：
Dalle, C;Eisenach, JC
通讯作者：
Eisenach, JC
影响因子：
5.5
作者：
Qiao, Guo-Fen;Li, Bai-Yan;Schild, John H.
通讯作者：
Schild, John H.
DOI：
10.1152/ajpregu.90401.2008
发表时间：
2008-10-01
影响因子：
2.8
作者：
Li, Bai-Yan;Qiao, Guo-Fen;Schild, John H.
通讯作者：
Schild, John H.