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Intermittent fluctuations in a single cardiac cell

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Abstract Book of the XXIII IUPAP International Conference on Statistical Physics, Genova, Italy, (9-13 July 2007)

Abstract

It is now widely accepted that a variety of physiological functions, including generation of action potentials in nerves and contraction of muscle, are cooperative phenomena of many molecular machines. The size of each molecular machine, such as an ion channel and a molecular motor, is typically several nanometers, and their behavior is intrinsically stochastic. In the last couple of decades, the properties of single molecular machines have been intensively investigated by use of newly developed single-molecule-detection techniques. In addition, much theoretical effort has also been made in order to account for their properties. As a consequence, knowledge on single molecular machines is being rapidly accumulated. On the basis of the achievements in single-molecule statistical physics, we believe that to understand the properties of complexes of molecular machines is now in scope. There remains a large vacancy to be explored between single molecules and macroscopic tissue. In particular, the behavior of a single cell has to be studied from a viewpoint of statistical physics, because cooperative phenomena of large but finite number of molecular machines may play important roles in the scale of a single cell. In this perspective, we are interested in the long-term behavior of a single cardiomyocyte (a heart muscle cell). Cardiomyocytes are the main constituent of a heart. It has been known that these cells exhibit periodic contraction when they are cultivated in vitro. The erlier studies on the culture of cardiomyocytes have concentrated on the dynamics of a cellular network, where many cells are tightly coupled to each other. However, the properties of a single cell, in particular its long-term behaviors, have not been paid much attention. We thus constructed an experimental system to monitor spontaneous contractions of a single isolated cardiomyocyte derived from newborn rats in a wide range of time scale. As a consequence, complex activities of a single isolated cardiomyocyte were observed. The timings of spontaneous contractions (beats) are found to fluctuate with a large magnitude. For a relatively short time scale (below several minites), the series of inter-beat intervals (IBIs) were found to be Poissonian. However, for larger time scales, on/off switching of activity was frequently observed. Off periods, where no spontaneous contraction is observed, sometimes range to several hours. The distribution of IBIs exhibits a power-law tail of a Lorentz type for large intervals. Furthermore, it was found that the time series of IBIs possess a scale-invariant correlation that is characterized as 1/f noise. These experimental findings imply that a single cardiomyocyte cannot be regarded as a simple limit cycle oscillator. We hope that further investigation of the long-term behavior of a single cell leads to understanding of cooperative phenomena of molecular machines inside a cell.

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