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超极化激活电流对大鼠有髓 A 型迷走传入神经元兴奋性的功能影响。

Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat.

机构信息

Department of Pharmacology, Harbin Medical University, Harbin, China.

出版信息

Clin Exp Pharmacol Physiol. 2010 Aug;37(8):852-61. doi: 10.1111/j.1440-1681.2010.05396.x. Epub 2010 Apr 26.


DOI:10.1111/j.1440-1681.2010.05396.x
PMID:20456426
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2995696/
Abstract
  1. The hyperpolarization-induced, cation-selective current I(h) is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia, but the peak magnitude and voltage- and time-dependent properties of this current vary widely across afferent fibre type. 2. Using patch clamp investigations of rat isolated vagal ganglion neurons (VGN) identified as myelinated A-type afferents, we established 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 I(h) using the current clamp technique. 3. Two robust responses were observed in response to hyperpolarizing step currents: (i) upon initiation of the negative step current, there was a rapid hyperpolarization of membrane potential followed by a depolarizing voltage sag (DVS) towards a plateau in membrane potential as a result of steady state recruitment of I(h); and (ii) 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 were strongly correlated (r(2) > 0.9) with a broad compendium of dynamic discharge characteristics in these A-type VGN. 4. In response to depolarizing step currents of increasing magnitude, the discharge frequency of the A-type VGN responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current, there was a post-excitatory membrane hyperpolarization of a magnitude that was strongly correlated with action potential discharge rate (r(2) > 0.9). 5. Application of the selective hyperpolarization-activated cyclic nucleotide gated (HCN) channel blockers ZD7288 (10 micromol/L) or CsCl (1.0 mmol/L) abolished I(h) and all of the aforementioned functional correlates. In addition to reducing the excitability of the A-type VGN to step depolarizing currents. 6. Because there is increasing evidence that the HCN channel current may represent a valid target for pharmacological intervention, the quantitative relationships described in the present study could potentially help guide the molecular and/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.
摘要
  1. 超极化诱导的阳离子选择性电流 I(h) 在迷走神经和背根神经节的周围感觉神经元中广泛观察到,但这种电流的峰值幅度和电压及时间依赖性特性在传入纤维类型上差异很大。
  2. 使用大鼠分离的迷走神经节神经元(VGN)的膜片钳研究,这些神经元被鉴定为有髓 A 型传入纤维,我们建立了一个功能概要,描述了由于使用电流钳技术控制 I(h) 的募集,膜电位变化与这些感觉神经元动态放电特性之间的关系。
  3. 在对超极化阶跃电流的反应中观察到两种稳健的反应:(i)在负阶跃电流开始时,膜电位迅速超极化,随后由于 I(h) 的稳态募集,膜电位出现去极化电压凹陷(DVS)并达到平台;(ii)在负阶跃电流终止时,膜电位迅速恢复到测试前的静息膜电位,这通常导致自发性动作电位放电。这些数据与这些 A 型 VGN 的广泛动态放电特性具有很强的相关性(r(2) > 0.9)。
  4. 随着递增幅度的去极化阶跃电流的反应,A 型 VGN 的放电频率以持续重复放电率的增加而增加。在去极化阶跃电流终止时,存在与动作电位放电率强烈相关的(r(2) > 0.9)后兴奋性膜超极化。
  5. 应用选择性超极化激活环核苷酸门控(HCN)通道阻滞剂 ZD7288(10 µm 时)或 CsCl(1.0 mmol/L)可消除 I(h) 和所有上述功能相关性。除了降低 A 型 VGN 对阶跃去极化电流的兴奋性。
  6. 由于越来越多的证据表明 HCN 通道电流可能是药理学干预的有效靶点,因此本研究中描述的定量关系可能有助于指导 HCN 通道门控特性的分子和/或化学修饰,以对 VGN 放电特性产生特定的结果,理想情况下,不仅仅是对特定 HCN 通道亚型的选择性阻断。

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[3]
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[4]
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[5]
Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats.

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[6]
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[7]
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本文引用的文献

[1]
IH current generates the afterhyperpolarisation following activation of subthreshold cortical synaptic inputs to striatal cholinergic interneurons.

J Physiol. 2009-12-15

[2]
Diabetes alters protein expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits in rat nodose ganglion cells.

Neuroscience. 2009-10-6

[3]
17Beta-estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats.

Am J Physiol Cell Physiol. 2009-9

[4]
HCN pacemaker channels and pain: a drug discovery perspective.

Curr Pharm Des. 2009

[5]
Enhancement of Ih, but not inhibition of IM, is a key mechanism underlying the PACAP-induced increase in excitability of guinea pig intrinsic cardiac neurons.

Am J Physiol Regul Integr Comp Physiol. 2009-7

[6]
Involvement of hyperpolarization-activated, cyclic nucleotide-gated cation channels in dorsal root ganglion in neuropathic pain.

Sheng Li Xue Bao. 2008-10-25

[7]
Role of the hyperpolarization-activated current Ih in somatosensory neurons.

J Physiol. 2008-12-15

[8]
Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat.

Am J Physiol Regul Integr Comp Physiol. 2008-10

[9]
Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels.

Am J Physiol Cell Physiol. 2008-8

[10]
Blunted excitability of aortic baroreceptor neurons in diabetic rats: involvement of hyperpolarization-activated channel.

Cardiovasc Res. 2008-9-1

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