DESCRIPTION (adapted from the applicant's description): The goal of this project and the long-term goal of the applicant is to mechanistically delineate structure, function, and regulatory mechanisms of the cardiac Na-Ca exchanger transporter. The cardiac Na-Ca exchanger protein is a target site for rational development of a novel class of pharmacological agents for potential use in treating congestive heart failure, diabetes, and sepsis. The investigators have identified a regulatory site on the cardiac Na- Ca exchanger protein. They have also developed a method for the expression of large-scale amounts of functional recombinant cardiac Na-Ca exchange protein in insect larvae (as an alternative to cultured cells) to facilitate analyses. This method makes practical a complete kinetic and structural analysis of recombinant mutant Na-Ca exchange activity in membrane vesicles. The investigators' goal is to topologically and functionally map the identified regulatory site and determine which amino acids are critical for drug binding and inhibition of the exchange process. The specific objectives of this project are to mutate amino acids in the regulatory site, express the recombinant mutant exchanger, evaluate the ability of the specific peptide ligand to inhibit the transport process, and evaluate regulation of mutant Na-Ca exchange activity for membrane phospholipids.
NIH ExPorter
NIH ExPorter