Peripheral artery diseases (PAD) increases muscle afferent nerve-activated reflex sympathetic nervous and blood pressure responses during exercise (termed as exercise pressor reflex). However, the precise signaling pathways leading to the exaggerated autonomic responses in PAD are undetermined. Considering that limb ischemia/reperfusion (I/R) is a feature of PAD, we determined the characteristics of acid-sensing ion channel (ASIC) currents in muscle dorsal root ganglion (DRG) neurons under the conditions of hindlimb I/R and ischemia of PAD. In particular, we examined ASIC currents in two distinct subpopulations, isolectin B -positive, and B -negative (IB4+ and IB4-) muscle DRG neurons, linking to glial cell line-derived neurotrophic factor and nerve growth factor. In results, ASIC1a- and ASIC3-like currents were observed in IB4- muscle DRG neurons with a greater percentage of ASIC3-like currents. Hindimb I/R and ischemia did not alter the distribution of ASIC1a and ASIC3 currents with activation of pH 6.7 in IB4+ and IB4- muscle DRG neurons; however, I/R altered the distribution of ASIC3 currents in IB4+ muscle DRG neurons with pH 5.5, but not in IB4- neurons. In addition, I/R and ischemia amplified the density of ASIC3-like currents in IB4- muscle DRG neurons. Our results suggest that a selective subpopulation of muscle afferent nerves should be taken into consideration when ASIC signaling pathways are studied to determine the exercise pressor reflex in PAD.
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