CLICs and GSTs: New Ion Channel Modulators

控制细胞内钙的浓度对细胞的正常功能至关重要。例如，肌肉细胞内钙浓度的短暂增加对肌肉收缩和正常心跳至关重要。这些钙被储存在细胞内的囊中，当需要时通过被称为ryanodine受体的钙通道迅速释放出来。我们已经发现细胞内的一些蛋白质（谷胱甘肽转移酶和细胞内氯离子通道蛋白）可以影响钙通过这些钙通道的量。这些蛋白质被认为有其他功能，我们发现它们对ryanodine受体钙通道的影响引起了相当大的兴奋。我们现在计划探索它们是如何做到这一点的。我们将改变蛋白质的特定区域，以发现哪些区域重要，哪些不重要。我们还将研究密切相关的蛋白质是否有类似的作用。我们正在研究的新型离子通道调节剂不仅能改变呼吸、运动和心脏收缩，还能改变心血管功能、神经元活动和免疫反应等方面。了解可溶性蛋白与离子通道相互作用的方式可能会揭示影响ryanodine受体钙通道功能的药物的新靶点，并允许合理设计特定药物来调节离子通道或离子通道调节剂。

Controlling the concentration of calcium inside cells is extremely important for normal cell function. For example, a brief increase in calcium concentration inside muscle cells is essential for muscle contraction and the normal heart beat. This calcium is kept stored in sacs inside cells and is rapidly released when needed through calcium channels known as ryanodine receptors. We have discovered that some proteins (glutathione transferases and intracellular chloride channel proteins) inside cells can affect how much calcium flows through these calcium channels. The proteins were thought to have other functions and our discovery of their effect on ryanodine receptor calcium channels has caused considerable excitement. We now plan to explore how they do this. We will mutate specific regions of the proteins to discover which regions are important and which are not. We will also look at whether closely related proteins have similar effects. The new class of ion channel modulator that we are studying has the capacity to alter not only respiration, movement and cardiac contraction, but also other aspects cardiovascular function, neuronal activity and immune responses. Understanding the way in which soluble proteins can interact with ion channels may reveal a novel target for drugs that affect ryanodine receptor calcium channel function and allow the rational design of specific drugs to regulate ion channels or ion channel modulators.