Mechanically-Evoked TRPV4-Mediated Currents Are Modulated by Activated Integrin β1

TRPV4 is a polymodal, non-selective cation channel which can be activated by mechanical stimuli only when they are applied directly at the cell-substrate interface. This restricted profile of mechanical activation suggests that mechanical gating of TRPV4 is highly dependent on either the specific physical context or molecular interaction partners within this cellular compartment. However, it is presently unknown what aspects of the cell-substrate interface confer mechanosensitivity to TRPV4. Integrin β1 has previously been indirectly linked to the mechanical activation of TRPV4 but this link has not yet been investigated in assays where it is clear that the gating stimulus was the mechanical input. We therefore aimed to test whether increasing integrin β1 activation could sensitise TRPV4-mediated, mechanically-evoked currents using whole-cell patch-clamp electrophysiology combined with a technique to apply mechanical stimuli directly at cell-substrate connections. We found that TRPV4-mediated currents were sensitised when integrin β1 was activated using the functional anti-integrin β1 [12G10] antibody. However, activation of integrin β1 using fibronectin-coated substrates only lead to minor increases in TRPV4 sensitivity. These data suggest that mechanical signalling via TRPV4 in the cell-substrate interface can be tuned by the activation state of integrin β1.