PIONEERING RESEARCH ON THE DYNAMICAL ASPECT OF STRUCTURE-FUNTION RELATIONSHIP IN ION CHANNELS

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Structuire-function studies of ion channels have greatly progressed in this decade owing to the conbination of molecular bilogical-and pacth clamp-techniques. However it seems still difficult to analyze the dynamical aspects of structure-function relationship in ion channels mainly because we do not know how to measure changes in the higher oder structure of channel molecules. The aim of the present research project was to find out a clue how to detect and estimate the higher order structural changes of channel molecules and to correlate them with channel functions. The team members have been divided into three sub-teams each of which conducted, A) structure-function of biological channels, B) structure-function of model channels, and C) development of new microscopy techniqes. The latter two subjects are particularly characteristic and important in this project. We could scceed to synthetize the world simplest structured channel molecules with ion selectivity or voltage dependecy, which may greatly help us to understand the dynamic structure-function correlation of channel molecules. In addition we have developed several remarkable microscopy techniques ; visualization of single fluorescent molecule, tracing and manipulation of of single channel motion, time-resolved fine structural analysis by the conbination of caged compounds and cryo-electron microscopy. We believe that this achievement would open up a way for the detailled analysis of dynamical aspects of structure-function correlation in ion channels.