Functional role of A-type potassium currents in rat presympathetic PVN neurones
Functional role of A-type potassium currents in rat presympathetic PVN neurones
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DOI：
10.1113/jphysiol.2007.134379
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发表时间：
2007-08-01
影响因子：
5.5
通讯作者：
Stern, Javier E.
中科院分区：
文献类型：
--
作者：
Sonner, Patrick A.;Stern, Javier E.
尽管室旁核（paraventricular nucleus，PVN）神经元支配延髓头端腹外侧区（rostral ventrolateral medulla，RVLM），在生理和病理条件下对交感神经功能的控制起着重要作用，但其确切的调控机制仍不完全清楚。在本研究中，我们评估了瞬时外向钾电流I-A是否在PVN-RVLM神经元中表达，表征了其生物物理学和药理学特性，并确定了其在这些神经元中塑造动作电位和放电的作用。从逆行标记的PVN-RVLM神经元获得的膜片钳记录表明，在这些神经元中存在4-AP敏感，TEA不敏感的电流，其生物物理特性与I-A一致。药理学阻断I-A通过增加其宽度和减缓其衰减时间过程来使静息V-m去极化和延长Na+动作电位持续时间。有趣的是，阻断I-A增加或减少PVN-RVLM神经元的放电活动，支持I-A差异调节的PVN-RVLM神经元亚群的存在。在所有情况下，I-A对放电活动的影响被广谱Ca 2+通道阻滞剂阻止。免疫组织化学研究表明PVN-RVLM神经元的I-A由Kv1.4和/或Kv4.3通道亚单位介导。总的来说，我们的研究结果表明，I-A在PVN-RVLM神经元中的存在，它积极地调节它们的动作电位波形和放电活动。这些研究支持I-A作为一个重要的内在机制控制神经元兴奋性在这个中央前交感神经元群体。
Despite the fact that paraventricular nucleus (PVN) neurones innervating the rostral ventrolateral medulla (RVLM) play important roles in the control of sympathetic function both in physiological and pathological conditions, the precise mechanisms controlling their activity are still incompletely understood. In the present study, we evaluated whether the transient outward potassium current I-A is expressed in PVN-RVLM neurones, characterized its biophysical and pharmacological properties, and determined its role in shaping action potentials and firing discharge in these neurones. Patch-clamp recordings obtained from retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA insensitive current, with biophysical properties consistent with I-A, is present in these neurones. Pharmacological blockade of I-A depolarized resting V-m and prolonged Na+ action potential duration, by increasing its width and by slowing down its decay time course. Interestingly, blockade of I-A either increased or decreased the firing activity of PVN-RVLM neurones, supporting the presence of subsets of PVN-RVLM neurones differentially modulated by I-A. In all cases, the effects of I-A on firing activity were prevented by a broad spectrum Ca2+ channel blocker. Immunohistochernical studies suggest that I-A in PVN-RVLM neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results demonstrate the presence of I-A in PVN-RVLM neurones, which actively modulates their action potential waveform and firing activity. These studies support I-A as an important intrinsic mechanism controlling neuronal excitability in this central presympathetic neuronal population.