Insulin Enhances The Activity Of TRPV4 Channels In Rat Small Dorsal Root Ganglion Neurons

Insulin is not only the hormone responsible for maintaining glucose homeostasis, but it also 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, to date, it remains unclear whether insulin potentiates the activity of TRPV4 channels in peripheral sensory neurons. As such, we hypothesized that insulin acutely enhances the function of TRPV4 channels in small DRG neurons. PURPOSE: The aim of this investigation was to determine the effects of insulin on the activity of TRPV4 channels in small DRG neurons. METHODS: Using in vitro whole-cell patch clamp recordings from cultured rat DRG neurons (Sprague-Dawley rat, n = 10, body weight: 299 ± 37 g), GSK1016790A (a selective TRPV4 agonist, 10 μM)-induced inward currents were measured. The following solutions were then applied locally into the recording bath: (1) HEPES buffered solution as the vehicle control or (2) 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) to confirm the involvement of insulin receptors. Five minutes after application of the test solutions, GSK1016790A-induced inward currents were measured again. RESULTS: The fold change in total charge transfer from before to after GSK1016790A application in the insulin trial (1.56 ± 0.79) was significantly greater than those in the HEPES (0.79 ± 0.40, P < 0.01) and GSK1838705 + insulin trials (1.00 ± 0.48, P < 0.05). Further, there was no significant difference between the HEPES and GSK1838705 + insulin trials (P = 0.750). CONCLUSIONS: The data suggests that insulin augments the function of TRPV4 channels, thus possibly contributing to the insulin-induced potentiation of mechanical sensation in small DRG neurons. Supported by NIH HL-151632 and JSPS 23KJ2207