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颈动脉体对化学信号的换能作用

Kumar B Sc P, Phil D

伯明翰大学医学院生理学系,伯明翰,B15 2TT

摘要

颈动脉体可以将低氧和血液中其它刺激信号(可能包括低血糖)转换成不同强度的传入神经放电,沿心肺和神经内分泌反射的传入途径进入中枢,形成反射环路。低氧可抑制颈动脉体Ⅰ型细胞中的多种K~(+)通道,这种作用可能有种属差异;K~(+)通道的抑制使膜电位去极化,启动电压依赖性Ca~(2+)内流,最后导致神经分泌和传入放电。离子通道对低氧的反应可能是通过间接途径发生的,因此近期的工作集中在研究颈动脉体Ⅰ型细胞中在低氧感受中起关键作用的其它蛋白质。虽然有人认为来源于线粒体和/或NADPH的活性氧(reactive oxygen species,ROS)起一定作用,但是它们在颈动脉体中转导低氧信号的证据还不足。目前正在对另外两种假设进行检验。第一种假设是血红素加氧酶2(haemoxygenase 2,HO--2)通过信号分子CO控制特殊K~(+)通道的活动,而CO的生成量与氧分压高低有关。第二种假设是认为细胞能量感受器腺苷酸活化蛋白激酶(AMP--activated protein kinase,AMPK)起作用;低氧时AMP/ATP比值升高,激活AMPK,从而抑制Ⅰ型细胞的K~(+)通道,传入放电增加。颈动脉体的细胞上具有丰富的对氧敏感的K~(+)通道,低氧感受这个重要的细胞活动可以通过多条途径进行,在总反应中每种蛋白质也可能起不同的作用,例如不同蛋白质对氧的亲合力不同等。关于颈动脉体感受低血糖的机制尚不清楚,但最近有证据提示,它并非由K~(+)通道关闭引起的,因此感受低血糖的机制和感受低氧的机制是不同的。

关键词： 颈动脉体; 化学受体; 低氧; 化学转换; 腺苷酸活化蛋白激酶; 葡萄糖

Translating blood--borne stimuli: chemotransduction in the carotid body

Kumar B Sc P, Phil D

Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TT

Abstract

The carotid body can transduce hypoxia and other blood-borne stimuli, perhaps including hypoglycaemia, into afferent neural discharge that is graded for intensity and which forms the afferent limb of a cardiorespiratory and neuroendocrine reflex loop. Hypoxia inhibits a variety of K~(+) channels in the type Ⅰ cells of the carotid body, in a seemingly species-dependent manner, and the resultant membrane depolarisation is sufficient to activate voltage-gated Ca~(2+) entry leading to neurosecretion and afferent discharge.The ion channels that respond to hypoxia appear to do so indirectly and recent work has therefore focussed upon identification of other proteins in the type Ⅰ cells of the carotid body that may play key roles in the oxygen sensing process. Whilst a role for mitochondrial and/or NADPH-derived reactive oxygen species (ROS) has been proposed, the evidence for their signalling hypoxia in the carotid body is presently less than compelling and two alternate hypotheses are currently being tested further. The first implicates haemoxygenase 2 (HO-2), which may control specific K~(+) channel activation through O_(2)-dependent production of the signalling molecule, carbon monoxide. The second hypothesis suggests a role for the cellular energy sensor, AMP-activated protein kinase (AMPK), which can inhibit type Ⅰ cell K~(+) channels and increase afferent discharge when activated by hypoxia-induced elevations in the AMP:ATP ratio. The apparent richness of O_(2)-sensitive K~(+) channels and sensor mechanisms within this organ may indicate a redundancy system for this vital cellular process or it may be that each protein contributes differently to the overall response, for example, with different O_(2) affinities.The mechanism by which low glucose is sensed is not yet known, but recent evidence suggests that it is not via closure of K~(+) channels, unlike the hypoxia transduction process.

Key words: Carotid body;chemoreceptor;Hypoxia;chemotransduction;AMP-activated protein kinase;Glucose

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引用本文：

Kumar B Sc P, Phil D. 颈动脉体对化学信号的换能作用[J]. 生理学报 2007; 59 (2): 128-132.

Kumar B Sc P, Phil D. Translating blood--borne stimuli: chemotransduction in the carotid body. Acta Physiol Sin 2007; 59 (2): 128-132 (in Chinese with English abstract).