Abstract
P2X(4) receptors are involved in mechanotransduction processes, but it is unknown whether or not P2X(4) receptors form mechanosensitive ion channels. This study questioned, whether laminar shear stress (LSS) can modulate P2X(4) receptor activity. Mouse P2X(4) receptor was cloned and heterologously expressed in Xenopus laevis oocytes. In two-electrode-voltage-clamp experiments the application of ATP (100μM) produced a transient inward current that was decreased by about 50% upon a second ATP application, corresponding to the desensitization behavior of P2X(4) receptors. In P2X(4) expressing oocytes LSS (shear forces of ~5.1dynes/cm(2)) did not produce any effect. However, LSS modulated the response of P2X(4) to ATP. With LSS (~5.1dynes/cm(2)) the desensitization of the current due to the second ATP application was diminished. Ivermectin (IVM), a compound which stabilizes the open state of P2X(4) receptors, mimicked the effect of LSS (~5.1dynes/cm(2)), since there was no additional effect of LSS after pre-incubation with IVM detected. This indicates that LSS like IVM stabilizes the open state of the receptor, although the particular mechanism remains unknown. These data demonstrate that LSS modulates the activity of P2X(4) receptors by eliminating the desensitization of the receptors in response to ATP probably by stabilizing the open state of the channel.