Real-time monitoring of cardiomyocyte activity using atomic force microscopy: a study of pacemaking activity and biological signals

The heart’s electrophysiology and the regulation of its activity offer a real challenge when it comes to understanding its relation to rhythmic cardiac contractility. Addressing those mechanisms at the cellular level is central to understanding cardiac pathophysiologies such as arrhythmia, and testing in vitro the potency or toxicity of new drugs on cardiac function. Several approaches have been reported to monitor cardiomyocyte activity in terms of frequency and amplitude. They include patch clamp monitoring of trans-membrane ionic currents, image analysis of phase contrast video microscopy, and fluorescence microscopy of intracellular calcium using fluorogenic probes such as Fluo-4 AM. Atomic force microscopy (AFM) has also been used as a force transducer, in order to quantify the beating frequency and amplitude of contraction, and to monitor cardiomyocyte activity in both spatial and temporal dimensions (Domke 1999)

Here, we used AFM to quantify the rhythmic/arrhythmic beating profile of a fully functional cardiomyocyte cell line (HL-1) exposed to pharmacological agents well-known to affect cardiovascular functions such as cardiac rhythm and output.

We have demonstrated that AFM-based force vs. time monitoring of cardiomyocyte pulsatile activity represents a powerful tool for studying the mechanism of action and functional effect of selective calcium and/or sodium ion channel blockers or agonists/antagonists of G-protein coupled receptors. Moreover, we showed that changes in the rhythmic/arrhythmic profile of cardiomyocyte allow the detection of functional membrane receptors not commonly linked to cardiac physiology such as the delta-opiod receptor.