Plasmalemmal Ca2+ signaling in arterial smooth muscle: it's elementary!
Plasmalemmal Ca2+ signaling in arterial smooth muscle: it's elementary!
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动脉平滑肌中的血浆膜Ca2+信号传导：这是基本的！
DOI：
10.1085/jgp.200609567
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发表时间：
2006-06
影响因子：
3.8
通讯作者：
Parker, Ian
中科院分区：
文献类型：
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作者：
Parker, Ian
在主要的细胞内第二信使中，钙是一种独特的元素;这是一个明显的声明，但对其信号功能具有深远的影响。作为一种元素，细胞不能合成或降解钙，它们只能主动地将钙从一个地方移动到另一个地方，让它被动地沿着浓度梯度移动，并让它与事物结合。主动移动是通过泵和转运蛋白完成的，它们在细胞溶质中非常低的基础游离[Ca 2 +]（50-100 nM）和细胞外液中高得多的浓度之间建立了巨大的（> 10，000倍）Ca 2+离子浓度梯度，并且储存在细胞内细胞器中，主要是ER或SR和线粒体中。质膜或细胞内膜中Ca 2+渗透通道的打开可引起局部胞质[Ca 2 +]的大幅和极快增加，因为Ca 2+离子被动地沿其电化学梯度流动（Hille，2001）。此外，Ca 2+信号可能在空间上以及时间上受到限制（Marchant和帕克，2000）。这是因为在大于几微米的距离处扩散变成相对缓慢的过程，并且因为Ca 2+离子在胞质溶胶中的扩散通过结合到固定缓冲液而进一步受到限制;尽管有趣的皱纹是由Ca 2+携带的信号（“消息”）实际上比离子本身（“信使”）传播得更快（Pando et al.，2006年）。因此，细胞已经进化出多种和复杂的Ca 2+信号库，其在空间和时间上比“分子”信使如环核苷酸更紧密地定位，所述环核苷酸更容易扩散并且在动力学上受到合成和降解的酶周转率的限制（Allbritton et al.，1992年）。在过去的十年或更长时间里，这种局部细胞内Ca 2+信号一直是人们非常感兴趣的主题;尤其是因为Ca 2+是我们目前可以用微米和毫秒分辨率成像的唯一第二信使。迄今为止最好的例子是通过三磷酸肌醇受体（IP 3R）和兰尼碱受体（RyR）从ER和SR释放Ca 2+离子产生的Ca 2+信号。这两种受体都形成Ca 2+渗透性通道，其具有显著的性质，即它们的开放由细胞内Ca 2+本身促进，导致Ca 2+诱导的Ca 2+释放（CICR）的再生机制。为了防止这一过程失控并产生全或无的全细胞应答，IP 3R和RyR通常排列在离散的簇中，允许分级产生信号，范围从单个通道的开放到单个通道的开放。（一般称为“基本”事件），通过当地CICR在一个集群中协调开放多个渠道（“基本”事件），到通过Ca 2+释放、扩散和CICR的连续循环在簇之间以跳跃方式传播的全球波（Berridge，1997）。基本事件，包括由IP 3 R介导的“喷烟”（帕克和姚，1991）和由RyR介导的“火花”（Cannell等人，1993），在许多细胞类型中作为细胞内Ca 2+信号的基本构件。例如，火花形成分级心肌收缩的局部控制模型的基础（Cannell等人，1993），并允许质膜Ca 2+依赖性K+通道的空间调节激活（Jaggar等人，1998年）。
Uniquely among the major intracellular second messengers, calcium is an element; an obvious statement, but one with profound consequences for its signaling functions. Being an element, cells cannot synthesize or degrade calcium, they can only actively move it from one place to another, allow it to move passively down concentration gradients, and let it bind to things. The active moving is done by pumps and transporters that establish enormous (> 10,000-fold) concentration gradients of Ca2+ ions between the very low basal free [Ca2+] in the cytosol (50–100 nM) and the much higher concentrations in the extracellular fluid and reservoirs sequestered in intracellular organelles, principally the ER or SR and mitochondria. Opening of Ca2+-permeable channels in the plasma or intracellular membranes can then evoke large and extremely rapid increases in local cytosolic [Ca2+] as Ca2+ ions flow passively down their electrochemical gradient (Hille, 2001). Moreover, Ca2+ signals may be spatially, as well as temporally, restricted (Marchant and Parker, 2000). This is because diffusion becomes a relatively slow process at distances greater than a few micrometers, and because diffusion of Ca2+ ions in the cytosol is further restricted by binding to immobile buffers; although an interesting wrinkle is that the signal carried by Ca2+(“message”) actually travels faster then the ions themselves (the “messengers”)(Pando et al., 2006). Cells have thus evolved a diverse and complex repertoire of Ca2+ signals, which are more tightly localized in space and time than is possible with “molecular” messengers such as cyclic nucleotides that diffuse more readily and are kinetically limited by enzyme turnover rates of synthesis and degradation (Allbritton et al., 1992). Such local intracellular Ca2+ signals have been a subject of much interest over the last decade or more; not least because Ca2+ is the only second messenger we can presently image with micrometer and millisecond resolution. The best examples to date are provided by Ca2+ signals generated by liberation of Ca2+ ions from the ER and SR through inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR). Both of these receptors form Ca2+-permeable channels that have the notable property that their opening is promoted by cytosolicCa2+ itself, leading to a regenerative mechanism of Ca2+-induced Ca2+ release (CICR). To prevent this process getting out of hand and generating all-or-none whole cell responses, IP3R and RyR are typically arranged in discrete clusters, permitting a hierarchical generation of signals ranging from opening of individual channels (generically termed “fundamental” events), through the concerted opening of several channels in a cluster by local CICR (“elementary” events), to global waves that propagate in a saltatory fashion between clusters by successive cycles of Ca2+ release, diffusion, and CICR (Berridge, 1997). The elementary events, including “puffs” mediated by IP3R (Parker and Yao, 1991) and “sparks” mediated by RyR (Cannell et al., 1993), serve as the basic building blocks of intracellular Ca2+ signals in many cell types. For example, sparks form the basis for the local control model of graded cardiac muscle contraction (Cannell et al., 1993), and permit a spatially regulated activation of plasma membrane Ca2+-dependent K+ channels (Jaggar et al., 1998).