Characterize ASIC3 in Muscle Sensory Neurons with Femoral Artery Occlusion

Abstract

The sympathetic nerve activity and arterial blood pressure responses to static muscle contraction are greater in rats with femoral artery ligation, likely due to enhanced ASIC3 expression in thin muscle afferent nerves. The current study was to characterize acid‐induced current with activation of ASIC3 in DRG neurons of control rats and rats with 24 hrs of femoral occlusion using whole‐cell patch clamp methods. Also, existence of ASIC3 in DRG neurons of thin fiber afferents was examined. The DRG neurons were labeled by injecting the fluorescence tracer DiI into the hindlimb muscles. The data showed that ~90% of current responses evoked by pH 6.7 in DRG neurons are ASIC3‐like. The peak current amplitude to pH 6.7 is significantly attenuated with rAPETx2, a specific ASIC3 antagonist. In addition, ASIC3‐like current responses to pH 6.7 are seen in small, medium and large size of DRG neurons and the distribution of the size of DRG neurons is similar in both groups. However, the peak current amplitude of DRG neuron response induced by stimulation of ASIC3 is larger in occluded rats than that in control rats. Moreover, the percentage of DRG neurons with ASIC3‐like currents is greater after arterial occlusion compared with control. Furthermore, the data showed that femoral occlusion mainly augments expression of ASIC3 within DRG neurons projecting C‐fiber afferents. Overall, these data suggest that (1) the majority of current responses to pH 6.7 are ASIC3‐like in DRG neurons with nerve endings in the hindlimb muscles; (2) a greater acid‐induced current responding to pH 6.7 is developed as the blood supply to the hindlimb is deficient, and (3) increased ASIC3 is largely seen in C‐fiber of DRG neurons after the hindlimb ischemia.