Inducing Overdrive Suppression in Chicken Cardiomyocytes Using Photovoltaic Devices and Multielectrode Arrays

Cardiomyocytes exhibit rhythmic electrical activity originating from specialized pacemaker cells, leading to periodic contractions of the cardiac muscle. Disturbance of this periodic cardiac rhythm due to heart damage, stress or ischemia may lead to arrhythmic contractions, with possibly severe and life-threatening consequences [1]. However, the heart has various protective mechanisms to stabilize the cardiac rhythm. One of these mechanisms is called overdrive suppression, which is induced when cardiac tissue is depolarized at frequencies higher than its intrinsic beating rate [2]. The rapid stimulation overwhelms the electrical signaling of the cells, since intra- and extracellular ionic concentrations cannot return to normal levels between stimuli, leading to a momentary pause in the electrical activity [2]. It has been shown that different stimulation protocols affect the duration of this pause in activity in cardiac cell aggregates [2], but it is unclear how localized stimulation of the cells in one region affects the synchronized activity in monolayers of cardiac tissue as a whole. Investigating the causes of overdrive suppression may lead to new insights into the mechanisms of cellular excitability and ion channel dynamics.

In our research, we use custom photovoltaic devices based on a bulk heterojunction composite [3,4] and multielectrode arrays (MEAs) to investigate the effects of different stimulation protocols on cardiac tissue. Monolayers of embryonic chicken cardiomyocytes are cultured on the surface of photovoltaic electrodes, which can be used to induce spatially independent electrical charges in the cardiac tissue when stimulated with red light (660 nm) [3]. By varying the intensity and duration of light pulses, we can investigate the effects of different stimulation parameters on the spontaneous beating of the cardiac tissue. Similarly, cardiac monolayers are cultured on MEAs, which allow for localized stimulation as well as measurement of the electrical activity of cardiac cells. The spatiotemporal changes of the periodic contractions can be observed directly under the microscope or by measuring the changes in intracellular calcium concentrations using fluorescence imaging techniques. Video-based image analysis of selected regions of interest may then be used to track and quantify the contractions of the cardiac tissue [5]. By combining these modalities, we can observe the correlation between mechanical, electrical and calcium activity while the cardiac cells are stimulated to exhibit overdrive suppression.

References
[1] Antzelevitch and Burashnikov: Overview of basic mechanisms of cardiac arrhythmia. Cardiac Electrophysiology Clinics. 2011;3(1):23–45.
[2] Kunysz et al.: Overdrive suppression of spontaneously beating Chick Heart Cell Aggregates: Experiment and theory. American Journal of Physiology-Heart and Circulatory Physiology. 1995;269(3).
[3] Schmidt et al.: Light Stimulation of Neurons on Organic Photocapacitors Induces Action Potentials with Millisecond Precision. Adv. Mater. Technol. 2022, 7, 2101159.
[4] Polz et al.: Holistic Equivalent Circuit Model for Capacitive Extracellular Stimulation. Current Directions in Biomedical Engineering, Vol. 8 (Issue 2), pp. 777-780.
[5] Ahola et al.: Video image-based analysis of single human induced pluripotent stem cell derived cardiomyocyte beating dynamics using digital image correlation. BioMedical Engineering OnLine 2014 13:39.