The lectin LecA sensitizes the human stretch-activated channel TREK-1 but not Piezo1 and binds selectively to cardiac non-myocytes

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research was supported by the European Research Council (Advanced Grant CardioNECT, Project ID: #323099, PK) and a research grant from the Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin, #3091311631). Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). SAC are activated by stretch and changes in membrane curvature but their precise role in the heart is unclear. The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for bacterial cell invasion by inducing membrane curvature. We investigate whether LecA modulates SAC activity, namely TREK-1 and Piezo1 in human embryonic kidney (HEK) cells. Confocal microscopy and electron tomography were used to follow binding dynamics of LecA, and the ion channel activity was recorded using the patch-clamp technique. Additionally, freshly isolated cardiac cells were used for studies into cell type dependency of LecA binding. LecA binds within seconds to cell surface. Local plasma membrane invaginations are detected by 17 min of LecA exposure. LecA sensitizes TREK-1, but not Piezo1, to voltage and mechanical stimulation. In freshly isolated cardiac cells, LecA binds to non-myocytes, but not to cardiomyocytes from mouse, rabbit, pig, and human. Our results suggest that LecA may serve as a pharmacological tool to study cardiac SAC in a cell type-preferential manner. Abstract Figure. Graphical abstract

Mechanical Communication Between Cardiac Cell Leads to Synchrony in Beating

It is generally understood that cardiac cells synchronize their beating through electro-chemical signalling. Here we show, theoretically and experimentally, that isolated cardiac cells can communicate with each other through an intervening deformable media. Such communication leads to coupled dynamics and emergence of synchronous beating. The interaction between the cells depends inversely with the elastic modulus of the media, and the distance between them. This finding may explain asynchronous beating of the atrium in patients with atrial fibrillation where the stiffness of the atrial wall becomes significantly harder due to fibrosis [1].

Electrophysiology of the Sodium-Potassium-ATPase in Cardiac Cells

Like several other ion transporters, the Na+-K+ pump of animal cells is electrogenic. The pump generates the pump current I p. Under physiological conditions, I p is an outward current. It can be measured by electrophysiological methods. These methods permit the study of characteristics of the Na+-K+ pump in its physiological environment, i.e., in the cell membrane. The cell membrane, across which a potential gradient exists, separates the cytosol and extracellular medium, which have distinctly different ionic compositions. The introduction of the patch-clamp techniques and the enzymatic isolation of cells have facilitated the investigation of I p in single cardiac myocytes. This review summarizes and discusses the results obtained from I p measurements in isolated cardiac cells. These results offer new exciting insights into the voltage and ionic dependence of the Na+-K+ pump activity, its effect on membrane potential, and its modulation by hormones, transmitters, and drugs. They are fundamental for our current understanding of Na+-K+ pumping in electrically excitable cells.