Studies on molecular mechanism of neural calcium signaling

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Intracellular calcium ion plays critical roles in neural signaling and neural plasticity. Recently, application of molecular biological techniques into neurobiology has dramatically accelerated studies on molecular mechanism of calcium metabolism in the nervous system, and led to elucidation of functions and properties of proteins which work as functional elements. On the other hand, our knowledge of higher brain functions is also rapidly increasing, especially owing to non-invasive measurement methods. However, there still remains a big gap between understanding molecules in brain and understanding higher brain functions. In order to fill the gap, we studied following subject in this project.We studied molecular mechanism of modulation of voltage-dependent calcium channels through GTP-binding proteins, by electrophysiological-and pharmacological measurements of recombinant calcium channels expressed in cultured cells. We obtained novel observation indicating showing multiple mode of G-protein modulation. We investigated molecular interaction between voltage-dependent calcium channels and ryanodine receptors expressed in skeletal muscle cells derived from ryanodine receptor-deficient mice. We demonstrated functional non-equality between skeletal type and cardiac type of ryanodine receptors in the excitation-contraction coupling mechanism. We have been trying to clone a family of cDNAs encoding a novel type of non-voltage-dependent calcium permeable channels. So far we have obtained cDNAs of several members of this family, and now are now studying tissue distribution and functional properties. To meet the need for calcium imaging of mouse brain, we have made a setup designed for brain slice preparation and developed a software environment. The basic data of calcium metabolism of mouse neurons corresponds well to those of rat neurons, however, the small size of mouse brain makes it difficult to handle smaller structures or immature brains.