Microfluidic systems to examine intercellular coupling of pairs of cardiac myocytes

Klauke, N., Smith, G. and Cooper, J. M. (2007) Microfluidic systems to examine intercellular coupling of pairs of cardiac myocytes. Lab on a Chip, 7, pp. 731-739. (doi:10.1039/b706175g)

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Abstract

In this paper we describe a microfluidic environment that enables us to explore cell-to-cellsignalling between longitudinally linked primary heart cells. We have chosen to use pairs (or doublets) of cardiac myocyte as a model system, not only because of the importance of cell–cellsignalling in the study of heart disease but also because the single cardiomyocytes are both mechanically and electrically active and their synchronous activation due to the intercellular coupling within the doublet can be readily monitored on optical and electrical recordings. Such doublets have specialised intercellular contact structures in the form of the intercalated discs, comprising the adhesive junction (fascia adherens and macula adherens or desmosome) and the connecting junction (known as gap junction). The latter structure enables adjacent heart cells to share ions, second messengers and small metabolites (<1 kDa) between them and thus provides the structural basis for the synchronous (syncytical) behaviour of connected cardiomyocytes. Using the unique environment provided by the microfluidic system, described in this paper, we explore the local ionic conditions that enable the propagation of Ca<sup>2+</sup> waves between two heart cells. We observe that the ability of intracellular Ca<sup>2+</sup> waves to traverse the intercalated discs is dependent on the relative concentrations of diastolic Ca<sup>2+</sup> in the two adjacent cells. These experiments rely upon our ability to independently control both the electrical stimulation of each of the cells (using integrated microelectrodes) and to rapidly change (or switch) the local concentrations of ions and drugs in the extracellular buffer within the microfluidic channel (using a nanopipetting system). Using this platform, it is also possible to make simultaneous optical recordings (including fluorescence and cell contraction) to explore the effect of drugs on one or both cells, within the doublet.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Klauke, Dr Norbert and Smith, Professor Godfrey and Cooper, Professor Jonathan
Authors: Klauke, N., Smith, G., and Cooper, J. M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
College of Science and Engineering > School of Engineering > Electronics and Nanoscale Engineering
Journal Name:Lab on a Chip
Publisher:Royal Society of Chemistry
ISSN:1473-0197
ISSN (Online):1473-0189
Published Online:17 May 2007

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