Main Research Focus:
Membrane Targeting of Cardiac Ion Channels
The basic function of the heart is to work as a pump, circulating blood throughout the body. For each successful heartbeat, millions of individual heart cells must contract successfully and their activity must be coordinated with each other. A biological electrical system based on ion channels exists to regulate contraction and coordination. In diseased heart, damage from blocked arteries leads to improper cellular expression of these ion channels which contributes to both dangerous heart rhythms and congestive heart failure.
Because arrhythmias and heart failure are the primary causes of death and disability in the United States, we are very interested in the mechanisms of ion channel development and regulation in normal and damaged heart cells.
Channel Trafficking in Heart Disease
Ischemic heart disease results in congestive heart failure and arrhythmias that cause sudden cardiac death. The cellular pathophysiology of ischemic heart disease includes altered distribution of Cx43 based gap junctions and the L-type calcium channel (Cav1.2) from the normal locations in separate well defined subregions of the cardiac plasma membrane. Gap junctions, which exist at the longitudinal ends of cardiomyocytes, allow heart cells to communicate with each other, coordinating each heartbeat.
The L-type calcium channel exists mainly on the cardiomyocyte T-tubule system to trigger intracellular calcium release from the sarcoplasmic reticulum.
Abnormalities in the amount and localization of gap junction and L-type calcium channels lead to heart dysfunction. We are trying to understand the molecuar basis of gap junction and L-type calcium channel surface expression, and their altered regulation due to disease.