Dr. Ken Philipson
Cardiac excitation-contraction coupling
MRL 3-609
310-825-7679
kphilipson@mednet.ucla.edu
Research Interests:
My research focuses on the regulation of Ca2+ transport across heart cell membranes. Primarily, we focus on a specific transporter, the Na+-Ca2+ exchanger, important in controlling cardiac contractility. Several aspects of the Na+-Ca2+ exchange system are being investigated. These include structure-function studies, regulatory studies, and physiological studies using genetically altered mice. Site-directed mutagenesis studies are in progress to determine the ion translocation pathway through the protein. Mutants are analyzed electrophysiologically using a novel giant excised patch technique. In addition to transporting Ca2+, the exchanger is regulated by Ca2+ at a high affinity Ca2+ binding site on the intracellular surface of the exchanger. Studies in progress are defining this site at the molecular and structural level. We also study the physiological and pathophysiological properties of mice with genetically altered levels of the Na+-Ca2+ exchanger. Unique and surprising phenotypes have been obtained. In short, a variety of molecular biological, biochemical and physiological approaches are being utilized to study the function and role of an interesting and important membrane transport system.
Representative Publications:
Nicoll, D.A., Sawaya, M., Kwon, S., Cascio, D., Philipson, K.D. and Abramson, J.
The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif. J. Biol. Chem. 281:21577-21581, 2006.
Pott, C., Yip, M., Goldhaber, J.I. and Philipson, K.D.
Regulation of cardiac L-type Ca2+ current in Na+-Ca2+ exchanger knockout mice: functional coupling of the Ca2+ channel and the Na+-Ca2+ exchanger. Biophys. J. In press.
Ren, X., Nicoll, D.A. and Philipson, K.D.
Helix packing of the cardiac Na+-Ca2+ exchanger: proximity of transmembrane segments 1, 2 and 6. J. Biol. Chem. 281:22808-22814, 2006.
Nicoll et al., 2006
Ottolia et al., 2004
