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Influence of Extracellular Matrix Proteins on Volume‐Sensitive Osmolyte Anion Channels (VSOACs) in C2C12 Cells

Browe & Baumgarten (J. Gen. Physiol. 122:689–702, 2003) demonstrated that mechanical stretch of β1 integrin receptors led to activation of a stretch‐sensitive outwardly rectifying Cl− current in ventricular myocytes. The purpose of this study was to determine whether extracellular matrix (ECM) composition modulated the VSOACs elicited by hypotonic medium (HYPO; 215 mosm) in skeletal muscle derived C2C12 cells. Cells grown on Laminin (Lm) or Fibronectin (Fn) were compared to cells grown in the absence of a defined ECM (NM). Cl− currents were recorded in whole‐cell voltage clamped cells. Basal membrane currents in isotonic media (300 mosm) were larger in cells grown on Lm (12X) or Fn (3X) vs NM. Membrane currents recorded in HYPO were larger on Lm (1.5X) or Fn (2.2X) vs NM. These currents displayed outward rectification, reversed at ECl and inactivated at potentials > +60 mV. Additionally, the tamoxifen‐sensitive VSOACs activated more quickly on Fn and Lm. Pre‐incubation of cells with RGD blocking peptide, prior to growth on Fn, nearly returned HYPO membrane currents to NM levels. Therefore, ECM composition profoundly influences the biophysical properties and mechanisms of onset of VSOACs.