This award will support collaborative research in molecular neurobiology between Dr. John P. Merlie, Washington University and Dr. Emmanuel Jover, Unite de Membranes Biologiques et Toxines Animales, French National Center for Scientific Research, Marseille, France. Preliminary experiments employing cDNA cloning indicate the existence of at least four mRNA's for mouse brain Na channels and one for mouse muscle. The investigators propose to extend the screening of existing cDNA libraries to identify yet undiscovered sequences. In addition, mRNA specific probes will be derived from the cDNA clones and used to characterize mRNA distribution in tissues during development and in cell cultures derived from brain and muscle. Finally, they will begin to prepare full length clones for studies of function by expression. The group in Marseille will carry out RNA analysis. At Washington University Dr. Merlie will continue to screen for new cDNA clones, and to sequence the novel clones that are identified. Full length clones for expression will be prepared and expressed in fibroblasts for pharmacological study in Marseille. Dr. Merlie has made significant contributions to the field of sodium channel physiology and pharmacology. Dr. Jovet and his research group have extensive background in mouse development systems. The results of this project are expected to show how recombinant DNA and related techniques can be applied to the study of ion channels.