title: Bending of z-lines by mechanical stimuli: an input signal for integrin dependent modulation of ion channels?
abstract: 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.
authors: Department of Physiology, Martin-Luther-University Halle, Halle, Germany.
authors: V
authors: V
authors: Dyachenko
authors: A
authors: A
authors: Christ
authors: R
authors: R
authors: Gubanov
authors: G
authors: G
authors: Isenberg
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004548:Elasticity; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D016023:Integrins; D007473:Ion Channels