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Ursula Ravens
Stem cells and cardiomyocytes
Previous and current research
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: Immunostaining with cardiac specific troponin-T (cTn-T)
antibodies in contracting cells derived from mouse
skeletal-muscle-derivedprecursors of cardiac cells (SPOCs).
B:
Spontaneous action potentials from mouse SPOCs.
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 ion channel 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.
Future prospects and goals
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 is 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.
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 cardiomyocytes from healthy and diseased hearts. Our goal is to characterize disease-associated alterations with special emphasis on atrial fibrillation in order to define targets for drug action, that may lead to new therapeutic strategies.
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Selected publications
Zahanich I, Graf EM, Heubach JF, Hempel U, Boxberger S, Ravens U. (2005): Molecular and functional expression of voltage-operated calcium channels during osteogenic differentiation of human mesenchymal stem cells. J Bone Min Res;20:1637-1646
Graf EM, Bock M, Heubach JF, Boxberger S, Richter W, Schultz J-H, Ravens U. (2005): Tissue distribution of human Cav1.2 a1 subunit splice variant with a 75 bp insertion. Cell Calcium, 38:11-21
Heubach JF, Graf EM, Leutheuser J, Bock M, Balana B, Zahanich I, Christ T, Boxberger S, Wettwer E, Ravens U. (2004): Electrophysiological properties of human mesenchymal stem cells. J Physiol;554(Pt 3):659-672.
Dobrev D, Friedrich A, Voigt N, Jost N, Wettwer E, Christ T, Ravens U. (2005): The G-protein gated potassium current IK,ACh is consitutively active in patients with chronic atrial fibrillation. Circulation;112 :3697-3706.
Christ T, Boknik P, Wöhrl S, Wettwer E, Graf EM, Bosch RF, Knaut M, Schmitz W, Ravens U, Dobrev D. (2004): Mechanisms of L-type Ca2+ current downregulation in chronic human atrial fibrillation: Reduced L-type Ca2+ current density is associated with increased activity of protein phosphatases. Circulation;110:2651-2657
Wettwer E, Hála O, Christ T, Heubach JF, Dobrev D, Knaut M, Varró, Ravens U. (2004): Role of IKur in controlling action potential shape and contractility in the human atrium: Influence of chronic atrial fibrillation. Circulation;110:2299-2306