Activation of a G protein-coupled inwardly rectifying K+ current and suppression of Ih contribute to dexmedetomidine-induced inhibition of rat hypothalamic paraventricular nucleus neurons
Activation of a G protein-coupled inwardly rectifying K+ current and suppression of Ih contribute to dexmedetomidine-induced inhibition of rat hypothalamic paraventricular nucleus neurons
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DOI：
10.1097/01.anes.0000281916.65365.4e
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发表时间：
2007-10-01
期刊：
影响因子：
8.8
通讯作者：
Takasaki, Mayumi
中科院分区：
文献类型：
--
作者：
Shirasaka, Tetsuro;Kannan, Hiroshi;Takasaki, Mayumi
背景资料：据报道，α（2）-肾上腺素受体激动剂产生精氨酸加压素释放抑制、利尿和交感神经阻滞作用。然而，其中枢作用机制仍不完全清楚。下丘脑室旁核（PVN）神经元与去甲肾上腺素能突触直接接触，受超极化激活电流控制，称为I-h（H电流）。右旋美托咪定是一种高度选择性和强效激动剂，其对α 2肾上腺素受体对I-h的影响尚不清楚。本研究的目的是检测右美托咪定对参与精氨酸加压素释放和自主调节的室旁核神经元的影响。方法：作者采用大鼠脑片制备的全细胞膜片钳技术研究了右美托咪定对室旁核大细胞神经元膜特性和室旁核小细胞神经元I-n的影响。右美托咪定剂量依赖性超极化PVN大细胞神经元。在电压钳模式中，右旋美托咪啶诱导外向电流，逆转电位为-94 mV，并且这显示出取决于K+的外部浓度。Ba 2+或肽毒素tertiapin预处理可阻断右美托咪定诱导的超极化。右美托咪定的作用被α 2肾上腺素受体拮抗剂育亨宾阻断。右美托咪定剂量依赖性地抑制PVN小细胞神经元的I-h。Cs+预处理阻断了右美托咪定对I-h的抑制作用。育亨宾阻断右美托咪定对Ih的抑制作用。结论：右美托咪定通过激活G蛋白偶联内向整流K+电流抑制PVN大细胞神经元，通过抑制I-h抑制PVN小细胞神经元。
Background: alpha(2)-Adrenoceptor agonist has been reported to produce inhibition of arginine vasopressin release, diuresis, and sympatholytic effects. However, its mechanisms of central action remain incompletely understood. Hypothalamic Paraventricular nucleus (PVN) neurons, which are in direct contact with noradrenergic synapses and are controlled by the hyperpolarization-activated currents, are called I-h (H current). The effect of dexmedetomidine, a highly selective and potent agonist, at alpha(2) adrenoceptors on I-h is unknown. The purpose of this study was to examine the effects of dexmedetomidine on the PVN neuron, which is involved in the arginine vasopressin release and autonomic regulation.Methods: The authors investigated the effects of dexmedetomidine on the membrane properties in PVN magnocellular neurons and an I-n in PVN parvocellular neurons with a whole cell patch clamp technique using a rat brain slice preparation.Results: Dexmedetomidine dose-dependently hyperpolarized PVN magnocellular neurons. in the voltage clamp mode, dexmedetomidine induced an outward current, with a reversal potential of -94 mV, and this was shown to depend on the external concentration of K+. Pretreatment with Ba2+ or peptide toxin tertiapin blocked hyperpolarization induced by dexmedetomidine. The effect of dexmedetomidine was blocked by an alpha(2)-adrenoceptor antagonist, yohimbine. I-h was suppressed dose dependently by dexmedetomidine in PVN parvocellular neurons. Pretreatment with Cs+ occluded the I-h suppression by dexmedetomidine. Yohimbine blocked the Ih suppression by dexmedetomidine. The I-h sensitive to dexmedetomidine was weakly modulated by intracellular cyclic adenosine monophosphate.Conclusions: Dexmedetomidine inhibited PVN magnocellular neurons by activation of the G protein-coupled inwardly rectifying K+ current and inhibited PVN parvoceBular neurons by suppression of I-h.