Nervous and sensory system

Insulin sensitizes the mechanical responsiveness of small dorsal root ganglion (DRG) neurons.We previously reported that transient receptor potential vanilloid 4 (TRPV4) channels play a crucial role in mechanical sensation in sensory neurons innervating skeletal muscle.However, it remains unclear whether insulin potentiates the activity of TRPV4 channels in peripheral sensory neurons.[Aims] The aim of this investigation was to determine the effects of insulin on the activity of TRPV4 in small DRG neurons.[Methods] Using in vitro whole-cell patch clamp recordings from cultured rat DRG neurons, 10 M of a TRPV4 agonist (GSK1016790A)-induced inward currents were measured before and 5 min after the application of either HEPES buffered solution (vehicle control) or 5 U/mL insulin.We also pretreated the DRG neurons with 20 nM of an insulin receptor antagonist 2-4 h before the insulin trial (GSK1838705 + insulin).[Results] The fold change in total charge transfer from before to after GSK1016790A application in the insulin trial was significantly greater than those in the HEPES (P < 0.01) and GSK1838705 + insulin trials (P < 0.05).Further, there was no significant difference between the HEPES and GSK1838705 + insulin trials (P = 0.750).[Conclusions] Insulin augments the function of TRPV4 channels, thus possibly contributing to the insulin-induced potentiation of mechanical sensation in small DRG neurons.