Ion selectivity of stretch-activated cation currents in mouse ventricular myocytes

Abstract

Stretch-activated non-selective cation currents (I _SAC) constitute a mechanism that can induce cardiac arrhythmias. We studied I _SAC in mouse ventricular myocytes by stretching part of the cell surface between the patch-pipette and a motor-driven glass stylus. In non-clamped cells, local stretch depolarised and induced after-depolarisations and extrasystoles. In voltage-clamped cells (K⁺ currents suppressed) I _SAC activated by local stretch had a nearly linear voltage dependence and reversed polarity between −12 and 0 mV. Conductance G _SAC increased with the extent of local stretch. I _SAC was not a Cl⁻ current (insensitivity to replacement of Cl⁻ by aspartate⁻). I _SAC was not a Ca²⁺-activated current (insensitivity to 5 mM intracellular BAPTA). G _SAC was blocked by 5 µM GdCl₃ or by 75 mM extracellular (e.c.) CaCl₂. Removal of e.c. CaCl₂ increased G _SAC 2.5-fold, as if G _SAC were sensitive to Ca²⁺ and Gd³⁺. Replacement of 150 mM e.c. Na⁺ by 150 mM Cs⁺, Li⁺, tetraethylammonium (TEA⁺) or N-methyl d-glucosamine (NMDG⁺) yielded currents that suggested for the conductance a selectivity G _Cs>G _Na>G _Li>G _TEA>G _NMDG. I _SAC was suppressed by cytochalasin D, as if an intact F-actin cytoskeleton were necessary for activation of I _SAC.