TRPV1 ALTERS THE EXPRESSION AND ACTIVITIES OF P2X3 RECEPTORS IN MUSCLE DORSAL ROOT GANGLION NEURONS OF EXPERIMENTAL PERIPHERAL ARTERY DISEASE

In peripheral artery disease (PAD), metaboreceptors and mechanoreceptors in muscle afferent nerves contribute to accentuated sympathetic nerve activity and arterial blood pressure via a neural reflex. Particularly, muscle metabolites such as adenosine triphosphate and products of oxidative stress in active muscles respectively stimulate purinergic P2X3 receptors and transient receptor potential cation channel V1 (TRPV1) in muscle afferent nerves, inducing the reflex sympathetic and blood pressure responses. Previous studies indicated that P2X3 and TRPV1 have an interaction in regulating the neural functions of sensory nerves. Thus, we determined the effects of removal of TRPV1 on the expression and activities P2X3 in muscle dorsal root ganglion (DRG) neurons. An experimental PAD was induced by 72-hour femoral artery occlusion (FAO). Western blotting was used to examine the expression of P2X3 in DRGs. The whole cell patch clamp was used to examine currents evoked by activation of P2X using α, β-methylene ATP. Resiniferatoxin (RTX, intraperitoneal injection) was previously given to abolish TRPV1 in DRGs. In results, RTX significantly decreased the protein levels of P2X3 in DRGs and attenuated the density of transient P2X currents in muscle DRG neurons of FAO group. However, RTX amplified the density of sustained P2X currents in muscle DRG neurons and the effect was less in FAO group. In conclusion, TRPV1 alters the expression and activities of P2X3 in muscle afferent nerves. The regulatory effects of TRPV1 on the transient and sustained P2X currents appear to be different, likely as a part of mechanisms involved in autonomic responses of PAD.