Institute Institute Physiologie und… Herz- und… Nina D. Ullrich Forschung New Molecular Targets…

Forschung

New Molecular Targets for the Treatment of Cardiac Diseases and Cellular Remodeling

In this project we are interested in the molecular determinants that underlie cardiomyocyte remodeling in hypertrophy and arrhythmogenic diseases. Chronic stress affects intracellular signaling cascades that are under control of adrenergic receptors, resulting in maladaptive functional changes and significant alterations of the Ca2+ handling machinery of the cardiomyocyte.

We investigate the impact of stress-induced transcriptional changes on cardiac function at the level of sarcolemmal Ca2+-handling proteins and Ca2+ channels of the sarcoplasmic reticulum. Novel pharmacological compounds are tested for their capability of reversing pathological remodeling at the cellular level.

Cardiac excitation-contraction coupling and Ca2+ current properties. Left: Ca2+-induced Ca2+ release in adult ventricular cardiomyocytes. L-type Ca2+ currents are elicited by depolarization to different membrane potentials. In parallel, cytosolic Ca2+ levels are monitored in the line-scan mode using a Ca2+-sensitive fluorescent indicator. Right: activation and inactivation curves of the L-type Ca2+ channel under control conditions (black) and in the presence of two compounds with different effects on the channel kinetics (red, blue).