Ca(2+)-induced Ca(2+) release (CICR) mediated by sarcoplasmic reticulum resident ryanodine receptors (RyRs) has been well described in cardiac, skeletal and smooth muscle. In brain, RyRs are localised primarily to endoplasmic reticulum (ER) and have been demonstrated in postsynaptic entities, astrocytes and oligodendrocytes where they regulate intracellular Ca(2+) concentration ([Ca(2+)](i)), membrane potential and the activity of a variety of second messenger systems. Recently, the contribution of presynaptic RyRs and CICR to functions of central and peripheral presynaptic terminals, including neurotransmitter release, has received increased attention. However, there is no general agreement that RyRs are localised to presynaptic terminals, nor is it clear that RyRs regulate a large enough pool of intracellular Ca(2+) to be physiologically significant. Here, we review direct and indirect evidence that on balance favours the notion that ER and RyRs are found in presynaptic terminals and are physiologically significant. In so doing, it became obvious that some of the controversy originates from issues related to (i) the ability to demonstrate conclusively the physical presence of ER and RyRs, (ii) whether the biophysical properties of RyRs are such that they can contribute physiologically to regulation of presynaptic [Ca(2+)](i), (iii) how ER Ca(2+) load and feedback gain of CICR contributes to the ability to detect functionally relevant RyRs, (iv) the distance that Ca(2+) diffuses from plasma membranes to RyRs to trigger CICR and from RyRs to the Active Zone to enhance vesicle release, and (v) the experimental conditions used. The recognition that ER Ca(2+) stores are able to modulate local Ca(2+) levels and neurotransmitter release in presynaptic terminals will aid in the understanding of the cellular mechanisms controlling neuronal function.

中文翻译：

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突触前ryanodine受体的存在及其功能意义。

Ca（2 +）-诱导的Ca（2+）释放（CICR）的肌浆网驻地ryanodine受体（RyRs）介导了心脏，骨骼和平滑肌。在大脑中，RyRs主要定位于内质网（ER），并已在突触后实体，星形胶质细胞和少突胶质细胞中得到证实，它们调节细胞内Ca（2+）浓度（[Ca（2 +）]（i）），膜电位和各种第二信使系统的活动。最近，突触前RyRs和CICR对中枢和外周突触前终末功能（包括神经递质的释放）的贡献受到了越来越多的关注。但是，目前尚无普遍共识，认为RyRs局限于突触前末端，也不清楚RyRs调节足够大的细胞内Ca（2+）池在生理上具有重要意义。在这里，我们回顾直接和间接的证据，总的来说，这种观点支持在突触前末端发现ER和RyRs，并且在生理上具有重要意义。这样一来，显而易见的是，一些争议源于以下问题：（i）能够最终证明ER和RyRs物理存在的能力；（ii）RyRs的生物物理特性是否使其能够在生理上有助于突触前[Ca（2 +）]（i）的调节，（iii）ER Ca（2+）负载和CICR的反馈增益如何有助于检测与功能相关的RyRs，（iv）Ca（2+）从质膜扩散到RyRs以触发CICR以及从RyRs到活性区以增强囊泡释放的距离，以及（v）使用的实验条件。ER Ca（2+）存储能够调节局部Ca（2+）水平和突触前终端中的神经递质释放的认识将有助于理解控制神经元功能的细胞机制。