Research

Cardiac function in health and disease

This Lab has a long-time interest in the function and regulation of cardiac muscle, both its contractile and electrical activity. In particular, we study cardiac Na transporters that regulate cardiac contractility, growth, and ultimately myocyte death. Two cardiac transporters that generate electrical current, Na/Ca exchangers and Na/K pumps, we study with powerful patch clamp techniques.

Our Lab is perhaps best known for our studies of Na/Ca exchangers that are involved in the generation of important cardiac arrhythmias. However, such studies remain limited to understand transporters because they do not provide real measurements of ion transport.

The study of Na/H exchangers has always been limited by the fact that it is electroneutral and does not generate a membrane current. For these reasons, we developed improved methods to monitor ion fluxes independent of membrane currents in single patch clamped cells.

In brief, we employ ion selective microelectrodes that we oscillate back and forth a few microns from the membrane surface. From the ion gradients that are detected we can calculate ion fluxes.

In this way we have been able to analyze transporter stoichiometries and study electroneutral transporters such as Na/H exchangers in much better detail than heretofore. Our most recent work focusses on the regulation of cardiac Na/K pumps, specifically their activation and inactivation by cardiac metabolic activity.

Cardiac function in health and disease