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Selected Publication:
Freidl, P.
Frühe Veränderungen der Calcium Homöostase und Remodelling der T-Tubuli in ß1-transgenen Mäusen
[ Diplomarbeit/Master Thesis ] Graz Medical University; 2009. pp.78.
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- Authors Med Uni Graz:
- Advisor:
- Heinzel Frank
- Pieske Burkert Mathias
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- Abstract:
- Introduction: With a prevalence of up to 4%, heart failure is one of the most significant chronic diseases seen from a socio-economic point of view. Currently, only symptomatic therapy options are available and therefore it is important to do more detailed research on how heart failure develops. Sympathetic ß-adrenergic stimulation and calcium-induced calcium release control normal cardiac function; the transversal tubular system enables synchronous activity in cell contraction. In the case of heart failure, these systems are disordered. However, little is known about initial changes in the course of pathogenesis. The objective of this thesis is to examine initial changes in calcium homeostasis and t-tubules under chronic ß1-adrenergic stimulation. Methods: Transgenetically (TG) altered young mice showing a cardio-selective overexpression of ß1-adrenergic receptors that results in chronic sympathetic stimulation were used as animal models and were compared to wild-type (WT) mice. Myocardial cells were isolated by means of the Langendorff Perfusion System and incubated with Fluo-4 AM and Di-8-Anepps respectively. The cells were then stimulated under a confocal laser scanning microscope while recording the calcium transients. In addition, Z Stacks of XY images of the cells were recorded in order to depict the t-tubules. This was followed by an analysis of the transients synchrony and kinetics as well as a determination of the density of t-tubules. Results: Synchrony of calcium release was decreased in TG cells. Only 75.32% of cell regions showed an early release compared to 95.43% in WT cells (-21.1%). The time to reach the maximal intracellular [Ca2+] was 55.13ms and was thus highly significantly extended (WT 42.97ms, +28.3%). The same was true for the time to reach the mean local half-maximal intracellular [Ca2+] (+28.6%). TG cells showed a mild hypertrophy (+8.4% in cell length). Density of t-tubules was decreased (-9.5%), especially inside the cells (-11.5%). The mean area of single t-tubular structures proved to be strongly decreased in TG cells (29.9%). Conclusion: The time to reach the maximal systolic calcium concentration is extended in young mice with chronic ß1-adrenergic stimulation. This extension significantly correlates with a dysynchrony in intracellular calcium release during the systole. T-tubules of transgenic animals have a slightly lower density and a more irregular structure than those of wild-type mice.