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

Neveux I, Doe J, Leblanc N, Valencik ML. Influence of the extracellular matrix and integrins on volume-sensitive osmolyte anion channels in C2C12 myoblasts. Am J Physiol Cell Physiol 298: C1006-C1017, 2010. First published February 17, 2010; doi:10.1152/ajpcell.00359.2009.-The purpose of this study was to determine whether extracellular matrix (ECM) composition through integrin receptors modulated the volume-sensitive osmolyte anion channels (VSOACs) in skeletal muscle-derived 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 approximate to 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 beta(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.