Lab Prof. Volk

Cardiac ion channels

The key interest of this group is to identify cellular and molecular mechanisms that regulate the function and expression of cardiac ion channels and thereby lead to differences in action potential duration (APD) and contractility in the heart.

It is well established that regional differences in APD in different areas of the heart are of great importance for a normal course of repolarization. Within the left ventricular free wall, for example, APD is much longer in endocardial than in epicardial myocytes with the consequence that endocardial myocytes repolarize last, although they become depolarized first. Hence, the wave of excitation travels from endocardial to epicardial regions, while the wave of repolarization travels in the opposite direction.

Under pathological conditions, such as cardiac hypertrophy or failure, this well-organized sequence of events is altered which is thought to contribute to the increased risk of cardiac arrhythmia and sudden cardiac death of patients with cardiac hypertrophy or failure. In order to further understand the underlying mechanisms, this group investigates the regulation and pharmacology of ion channels (Na+,K+ and Ca2+ channels) that are responsible for cardiac excitation and repolarization by using animal models as well as tissue or cell culture. At present, the primary focus lies in the identification of signaling cascades that participate in the regulation of those ion channels under pathophysiological conditions. A promising target is the cardiac mineralocorticoid receptor which participates in the regulation of cardiac Ca2+ and K+ channels.

It is hoped that a more detailed characterization of cardiac ion channels will lead to a better understanding of the mechanisms underlying cardiac repolarization and will help to develop therapeutic strategies to influence the organization of repolarization and hence prevent the development of malignant arrhythmia.