TRPA1 Function in Skeletal Muscle Sensory Neurons Following Femoral Artery Occlusion.

BACKGROUND/AIMS: Transient receptor potential channel A1 (TRPA1) is engaged in amplified autonomic responses evoked by stimulation of muscle afferent nerves in rats with experimental peripheral arterial disease. The purposes of this study were to characterize current responses induced by activation of TRPA1 in dorsal root ganglion (DRG) neurons of control limbs and limbs with femoral artery occlusion.

METHODS: DRG neurons from rats were labeled by injecting the fluorescence tracer DiI into the hindlimb muscles and whole-cell patch clamp experiments were performed to determine TRPA1 currents.

RESULTS: Data show that AITC (a TRPA1 agonist) from the concentrations of 50 µM to 200 µM produces a dose-dependent increase of amplitudes of inward current responses. Notably, the peak current amplitude induced by AITC is significantly larger in DRG neurons of ligated limbs than that in control limbs. AITC-induced current responses are observed in small and medium size DRG neurons, and there is no difference in size distribution of DRG neurons between control limbs and ligated limbs. However, femoral occlusion increases the percentage of the AITC-sensitive DRG neurons as compared to control. AITC-induced currents in DRG neurons are significantly attenuated by exposure to 10 µM of HC-030031, a potent and selective inhibitor of TRPA1, in both control and femoral occlusion groups. In addition, capsaicin (a TRPV1 agonist) evokes a greater increase in the amplitude of AITC-currents in DRG neurons of ligated limbs than that in control limbs.

CONCLUSIONS: A greater current response with activation of TRPA1 is developed in muscle afferent nerves when hindlimb arterial blood supply is deficient under ischemic conditions; and TRPV1 is partly responsible for augmented TRPA1 responses induced by arterial occlusion.