Activation of rat transient receptor potential cation channel subfamily V member 1 channels by 2-aminoethoxydiphenyl borate

BACKGROUND: The transient receptor potential cation channel subfamily V member 1 (TRPV1) channel has been proved to be a molecular integrator of inflammatory pain sensation. 2-Aminoethoxydiphenyl borate (2-APB) and its analogs have been noticed as attractive candidates for the development of a selective TRPV1 agonist and/or antagonist. However, selectivity and effectiveness, species dependence, and the binding site(s) of 2-APB on TRPV1 channel protein remain controversial. METHODS: The present study aimed to characterize acting sites of 2-APB on heterologously expressed rat TRPV1 (rTRPV1) channels in HEK 293 cells. Rat TRPV1 currents were recorded by cell-free, excised patch clamp techniques. RESULTS: In inside-out and outside-out patch modes, 2-APB applied either side of the membrane dose-dependently activated rTRPV1 channels. 2-APB dose-dependently potentiated rTRPV1 currents, that activated by capsaicin, protons, or noxious heat. 2-APB potentiated the capsaicin-activated rTRPV1 current from both side of the patch membrane. A structural analogue of 2-APB, diphenylboronic anhydride, showed the same potentiation effect on the capsaicin-activated rTRPV1 current. CONCLUSION: It is suggested that 2-APB directly opens rTRPV1 channels from both sides of the membrane and potentiates the opening of channels by inflammatory stimuli.