Cardiac Signals

The MEA system can be used for in vitro studies of the electrical properties of cardiac myocytes and, for example, effects of drug candidates on field potential waveforms and kinetics.

Primary cardiac myocytes can be easily harvested from fertilized chicken eggs, or from neonatal rat or mouse. It is also possible to obtain murine and human embryonic stem cells derived from embryoid bodies. There is also one cardiomyocyte cell line from mouse that retains a differentiated cardiac myocyte phenotype: HL-1 from Dr. W. Claycomb.

Plated cells form a syncytium and start beating spontaneously after a couple of days, or contract after electrical stimulation (pacing). The two-dimensional MEA layout is ideally suited for showing the waveform propagation and measuring the conduction velocity in a cardiomyocyte culture.

Simultaneous recordings of action potentials (with intracellular electrodes) and field potentials (with extracellular electrodes) have shown that there is a correlation between the rise time of the cardiac action potential (AP) and field potential (FP) as well as between AP and FP duration. A correlation between the waveform components and the ion channel activities was shown by using ion channel blockers or by depleting the medium of the respective ions.

(Reference: "Determination of Electrical Properties of ES Cell-derived Cardiomyocytes Using MEAs", Jürgen Hescheler et al., Journal of Electrocardiology, Vol. 37 Supplement 2004; "Estimation of Action Potential Changes from Field Potential Recordings in Multicellular Mouse Cardiac Myocyte Cultures", Marcel D. Halbach et al., Cell Physiol Biochem 2003;13:271–284).

The high and short peak of the extracellular field potential can be correlated to the rapid component of the depolarizing sodium current. The following plateau follows the time course of the slow calcium current; and the following positive or negative peak correlates to the slow rectifying K+ current (IKr). The polarity of this peak depends on several parameters, for example, the proximity of the cell layer to the measuring electrode, and cannot be predicted, but this fact does generally not matter for this assay.

The field potential duration corresponds to the action potential duration, which can be correlated to a QT interval in an electrocardiogram. It is measured from minimum of the Na+ peak to the maximum/minimum of the IKr current peak.

The effects of tested drugs on QRS duration and amplitude, local activation time, T wave amplitude, time of maximal slope of T wave, QT interval duration, and ARI (activation refractory interval) can be analyzed with the MEA System.

Typical applications are:

• Drug testing for effects on cardiac signal waveforms, for example QT prolongation
• Analysis of changes in the signal propagation kinetics
• Cocultures of stem cells and primary cells for basic research and for gaining insights into transplantation options and techniques
• Characterizations of cells for cardiac properties, for example of cardiomyocytes derived from stem cells

You will see in the tutorial how a virtual rack is set up for those purposes, and how typical signal waveforms look like.