Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents.

Acid-sensing ion channels (ASICs) play a critical role in nociception in human sensory neurons. Four genes ( and ) encoding multiple subunits through alternative splicing have been identified in humans. Real time-PCR experiments showed strong expression of three subunits , , and in human dorsal root ganglia; however, their detailed expression pattern in different neuronal populations has not been investigated yet. In the current study, using an hybridization approach (RNAscope), we examined the presence of , , and mRNA in three subpopulations of human dorsal root ganglia neurons. Our results revealed that and were present in the vast majority of dorsal root ganglia neurons, while was only expressed in less than half of dorsal root ganglia neurons. The distribution pattern of the three subunits was the same across the three populations of dorsal root ganglia neurons examined, including neurons expressing the REarranged during Transfection (RET) receptor tyrosine kinase, calcitonin gene-related peptide, and a subpopulation of nociceptors expressing Transient Receptor Potential Cation Channel Subfamily V Member 1. These results strongly contrast the expression pattern of in mice since our previous study demonstrated differential distribution of among the various subpopulation of dorsal root ganglia neurons. Given the distinct acid-sensitivity and activity dynamics among different ASIC channels, the expression differences between human and rodents should be taken under consideration when evaluating the translational potential and efficiency of drugs targeting ASICs in rodent studies.