ANALYSIS OF MOLECULAR MOVEMENTS IN CARDIAC MYOCYTES

ABSTRACT

This dissertation explores the fascinating world of cardiac function and dysfunction. Through application of various experimental and computational techniques new insights into aspects of intracellular diffusion restrictions, causes of hypertrophy, and development of cardiac energetics are gained. Experiments on rat cardiomyocytes using raster image correlation spectroscopy (RICS) reveal a counterintuitive result, whereby diffusion of a smaller fluorescent molecule is restricted more than that of a larger one, when comparing diffusion in the cytosol to that in solution. A stochastic computational model of diffusion is applied to find a possible explanation for this result. Modeling results suggest the existence of regularly placed semi-permeable barriers in the cardiomyocyte situated ~1 μm apart and having very low permeabilities. Such structures in the intracellular environment could enact a significant role in the function of cardiomyocytes, as well as in dysfunctional states of the heart. Also  discussed are experiments probing the causes of hypertrophic cardiomyopathy with the aim of studying mutations that affect signalling cascades and cause abnormalities in cardiomyocyte calcium handling.

SUPERVISOR: Marko Vendelin

OPPONENTS

• Pasi Tavi, Deparment of Biotechnology and Molecular Medicine, University of East Finland, Kuopio, Finland
• Allen Kaasik, Department of Pharmacology, University of Tartu, Tartu, Estonia

TIME OF DEFENSE

23 February 2012 at 13:00 in the Institute of Cybernetics, room B101

THESIS PDF: Analysis of molecular movements in cardiac myocytes

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