Sodium-level-sensitive sodium channel and salt-intake behavior
Sodium-level-sensitive sodium channel and salt-intake behavior
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DOI：
10.1093/chemse/bjh105
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Hiyama, TY
中科院分区：
文献类型：
--
作者：
Noda, M;Hiyama, TY
当体液中水和钠之间的正确平衡被破坏时，哺乳动物会感到口渴或对盐产生胃口，但人们对大脑中控制盐稳态的机制知之甚少。有人推测，渗透压感受器和特定的钠受体的存在都需要适应实验数据(Johnson和Edwards，1990；Denton等人，1996)。已经报道了几种候选渗透压受体(Oliet and Bourque，1993；Wells，1998；Liedtke et al.，2000)；然而，还没有鉴定出特定的钠受体。NAX通道-以前称为NAG/SCL11(大鼠)，NAV2。3(在小鼠体内)和NAV2。1(在人类中)-已被归类为电压门控钠通道的一个亚家族(Goldin等人，2000年)。然而，Nax的一级结构明显不同于其他电压门控钠通道家族成员，并且包括电压敏感和失活关键区域的差异。由于在异源系统中诱导Nax功能表达的所有尝试都失败了，因此对该通道的功能特性了解很少。几年前，我们通过在框内插入LacZ基因而使Nax基因被敲除的小鼠发现，Nax通道在脑室周围器官(CVO)的细胞中表达(Watanabe等人，2000)，特别是穹隆下器(SFO)和终板血管(OVLT)，这是控制体液离子平衡的重要区域；有关CNS以外的表达(见Watanabe等人，2002)。在口渴条件下，Nax缺陷小鼠表现出这两个区域神经元的过度活动，并摄入过量的盐分：野生型小鼠在脱水条件下喝水并停止摄入盐分。将高渗钠溶液注入脑室也引起了广泛的水摄取和对生理盐水(0.3M)的厌恶
Mammals feel thirsty or develop an appetite for salt when the correct balance between water and sodium in the body fluid has been disrupted, but little is known about the mechanism in the brain that controls salt homeostasis. It has been postulated that the existence of both an osmoreceptor and a specific sodium receptor is required to accommodate the experimental data (Johnson and Edwards, 1990; Denton et al., 1996). Several candidate osmoreceptors have been reported (Oliet and Bourque, 1993; Wells, 1998; Liedtke et al., 2000); however, a specific sodium receptor has not been identified. The Nax channel—formerly called NaG/SCL11 (in rats), Nav2. 3 (in mice) and Nav2. 1 (in humans)—has been classified as a subfamily of voltage-gated sodium channels (Goldin et al., 2000). The primary structure of Nax, however, markedly differs from that of other voltage-gated sodium channel family members and includes differences in the key regions for voltage sensing and inactivation. The functional properties of the channel are poorly understood, as all attempts to induce functional expression of Nax in heterologous systems have failed.Several years ago, we generated mice in which the Nax gene was knocked-out by insertion of the lacZ gene in-frame and found that the Nax channel is expressed in cells in the circumventricular organs (CVOs)(Watanabe et al., 2000), in particular the subfornical organ (SFO) and organum vasculosum lamina terminalis (OVLT), which are important regions for the control of body fluid ionic balance; for the expression other than the CNS (see Watanabe et al., 2002). Under thirst conditions, Nax-deficient mice showed hyperactivity of the neurons in these two areas and ingested excessive salt: Wild-type mice take water and stop salt ingestion under dehydrated condition. Infusion of a hypertonic Na solution into the cerebral ventricle also induced extensive water intake and aversion to saline (0.3 M