Influence of the extracellular matrix and integrins on volume-sensitive osmolyte anion channels in C2C12 myoblasts

摘要

The purpose of this study was to determine whether extracellular matrix (ECM) composition through integrin receptors modulated the volumesensitive osmolyte anion channels (VSOACs) in skeletal musclederived C2C12 cells. Cl - currents were recorded in whole cell voltage-clamped cells grown on laminin (LM), fibronectin (FN), or in the absence of a defined ECM (NM). Basal membrane currents recorded in isotonic media (300 mosmol/kg) were larger in cells grown on FN (3.8-fold at +100 mV) or LM (8.8-fold at +100 mV) when compared with NM. VSOAC currents activated by cell exposure to hypotonic solution were larger in cells grown on LM (1.72-fold at +100 mV) or FN (1.75-fold at +100 mV) compared with NM. Additionally, the kinetics of VSOAC activation was ≈27% quicker on FN and LM. These currents were tamoxifen sensitive, displayed outward rectification, reversed at the equilibrium potential of Cl - and inactivated at potentials +60 mV. Specific knockdown of β 1-integrin by short hairpin RNA interference strongly inhibited the VSOAC Cl - currents in cells plated on FN. In conclusion, ECM composition and integrins profoundly influence the biophysical properties and mechanisms of onset of VSOACs.