Our results suggest that the two TREK-like channels found in rat cardiomyocytes may reflect two different operating modes of TREK-1. The novel low-conductance channels described here may represent the major operating mode of TREK-1. The current flowing through mechanogated TREK-1 channels may serve to counterbalance the inward current flowing through stretch-activated non-selective cation channels during the filling phase of the cardiac cycle and thus to prevent the occurrence of ventricular extrasystoles.
We studied which components of mechanical cell deformation are involved in "stretch modulated ion currents" (SMIC). Murine ventricular myocytes were attached to glass coverslips and deformed in x, y and z with a 16 microm thin glass stylus (S) of calibrated stiffness. Three-dimensional confocal microscopy characterized cell deformation (T-tubular membranes, mitochondria) and bending of S (indicative of the applied force). Axial (x-) displacement of S sheared the upper cell part versus the attached bottom, close to S, it changed sarcomere length and bent z-lines ("z-line displacement"). Vertical (z-press) or transversal (y-shear) displacement of S bulged cytoplasm and mitochondria transversally without detectable z-line displacement. Axial stiffness increased with the extent of stress ("stress stiffening"). Depolymerization of F-actin or block of integrin receptors reduced stiffness. SMIC served as a proxy readout of deformation-induced signaling. Axial deformation activated a non-selective cation conductance (Gns) and deactivated an inwardly rectifying K+ conductance (GK1), z-press or y-shear did not induce SMIC. Depolymerization of F-actin or block of integrin receptors reduced SMIC. SMIC did not depend on changes in sarcomere length but correlated with the extent of z-line bending. We discuss that both shear stress at the attached cell bottom and z-line bending could activate mechanosensors. Since SMIC was absent during deformations without z-line bending we postulate that z-line bending is a necessary component for SMIC signaling.
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