CLICs and GSTs: New Ion Channel Modulators

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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.