Ursula Ravens, MD, PhD

Physiological and pharmacological responses in health and disease

Stem cells, progenitor cells and native cardiomyocytes

Drugs affecting physiology and pathophysiology of detrusor muscle

Previous and current research

Cardiac electrophysiology in health and disease

Bioelectrical activity of the heart is a prerequisite for its proper functioning as a pump. Heart disease as for instance hypertrophy and heart failure, is accompanied by an increased risk for fast and irregular cardiac rhythm which may even deteriorate to lethal arrhythmias. The patch clamp methods allows to study bioelectrical activity at the cellular level, to characterize its regulation in health and disease, and to identify targets for pharmacological intervention. Because of known species differences, our main interest is directed towards the study of human myocardial tissue and includes clinically relevant topics like electrical remodeling in atrial fibrillation and drug interactions with cellular targets.

Stem cells and tissue engineering

Heart muscle cells are fully differentiated with little potential to regenerate. Ischaemic damage during myocardial infarction results in irreversible loss of tissue that is replaced by functionally inactive scar tissue. We have studied various stem and progenitor cell types under conditions that will promote differentiation toward myogenic cell lines. A conditioning bioreactor has been designed for exploring the effects of physical stimuli such as regular mechanical stretch on cell growth and differentiation.

Drugs affecting physiology and pathophysiology of detrusor muscle

Pharmacological treatment of overactive bladder and lower urinary tract syndrome requires a thorough understanding of contractile function of urinary bladder smooth muscle cells. We study the effects of antimuscarinic and -adrenoceptor agonists on contractile activity and electrophysiology of isolated detrusor preparations from man, pig and mouse.

Future projects and goals

Almost every cell of the body possesses voltage-dependent ion channels that contribute to the regulation of cell function. We study the expression of ion channels, their accessory subunits and the currents they conduct in myocytes from healthy and diseased hearts. Our goal is to characterize disease-associated alterations in order to define targets for drug action, that may lead to new therapeutic strategies.

We plan to isolate and characterize cardiac stem cells and their precursors as a source of cells that may promote the repair of injured heart muscle. As stem cells differentiate into cardiomyocytes, expression and function of ion channels adapt to the new phenotype and ion channel activity measured with patch clamp techniques. For cells to be used in tissue engineering it is essential to know their responses to physiological and pharmacological stimuli.

The processes that control detrusor contraction and relaxation with special emphasis on the modulating role of the urothelium are going to be examined in various species. We will introduce a mouse model of urodynamics for the in-vivo study of drug effects.