A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract
A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract
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DOI：
10.1073/pnas.1431233100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Szurszewski, JH
中科院分区：
文献类型：
--
作者：
Farrugia, G;Lei, S;Szurszewski, JH
一氧化碳（CO）被认为是一种生理信使。CO激活cGMP并对钾通道有直接影响。CO的这两种作用都导致细胞静息膜电位的超极化，这表明CO可能起着超极化因子的作用，尽管仍然缺乏直接的证据。在这里，我们利用已知的膜电位梯度存在于胃肠道的肌肉层，以确定是否CO是一个内源性超极化因子。我们发现，血红素加氧酶-2-null小鼠有去极化平滑肌细胞，并在肠道的膜电位梯度被废除。外源性CO使膜电位超极化。犬胃肠道的超极化区域比去极化区域产生更多的CO并具有更高的血红素加氧酶活性。我们的研究结果表明，CO是一个关键的超极化因子所需的维持肠平滑肌膜电位和梯度。
Carbon monoxide (CO) is proposed as a physiological messenger. CO activates cGMP and has a direct effect on potassium channels. Both actions of CO lead to hyperpolarization of a cell's resting membrane potential, suggesting that CO may function as a hyperpolarizing factor, although direct evidence is still lacking. Here we take advantage of the known membrane potential gradient that exists in the muscle layers of the gastrointestinal tract to determine whether CO is an endogenous hyperpolarizing factor. We find that heme oxygenase-2-null mice have depolarized smooth muscle cells and that the membrane potential gradient in the gut is abolished. Exogenous CO hyperpolarizes the membrane potential. Regions of the canine gastrointestinal tract that are more hyperpolarized generate more CO and have higher heme oxygenase activity than more depolarized regions. Our results suggest that CO is a critical hyperpolarizing factor required for the maintenance of intestinal smooth muscle membrane potential and gradient.