Isolated Cardiomyocytes: Mechanosensitivity of Action Potential, Membrane Current and Ion Concentration

Excerpt

Isolated cardiomyocytes can be mechanically stretched by a variety of methods that are reviewed. The cell's electrophysiological response to a homogeneous axial stretch is relatively small, however, it is large during a local stretch that applies an additional shear stress component. If not voltage-clamped, cardiomyocytes respond local stretch with membrane depolarization, prolongation of the action potential duration and eventually with extra systoles. Under voltage clamp, local stretch induces an inward current (I_SAC) through non-selective channels and it deactivates the inwardly rectifying K⁺ current (I_K1), both changes contributing to the arrhythmogenicity. I_SAC is reviewed in terms of ion selectivity and mechanosensitivity. Putative activation mechanisms require an intact cytoskeleton, details, however, are speculative at present. Stretch increases the concentrations of Na⁺ and Ca²⁺ in the cytosol and in the cell organelles, partly because of the Na⁺- and Ca²⁺ influx carried by I_SAC. The modulation of long-lasting stretch on development of hypertrophy and cardiac failure are not included in this review. Instead, the consequences of stretch-induced ion accumulation are discussed in regard to the slow component of the force staircase, and the consequence of stretch-modulated currents in terms of stretch-induced arrhythmias.