IMAGING MOLECULAR STRUCTURE & ACTIVITY OF GAP JUNCTIONS

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DESCRIPTION: The experiments proposed by the investigator seek a better understanding of the quaternary structure of cardiac gap junction channels. To this end Atomic Force Microscopic (AFM) measurements will be made on hydrated cardiac gap junctions to determine the size, shape, subunit arrangement, subunit number, and general microstructure. These structures of fully formed gap junctions will be compared for reconstituted, purified and intact proteins. Additional measurements of connexon pairs will be compared to those obtained for isolated hemichannels to determine how the pairs are assembled during and prior to cell-cell contact. Finally, the investigator will utilize AFM measurement to begin unravelling the conformational changes which are associated with changes in the state of channel function. Open and closed states of the protein will be ascertained and compared to establish whether gross changes in morphology are associated with the transitions between the different functional states.