Large Acid-Evoked Currents, Mediated by ASIC1a, Accompany Differentiation in Human Dopaminergic Neurons

Research output: Contribution to journalResearch articleContributedpeer-review


  • Andreas Neuhof - , RWTH Aachen University (Author)
  • Yuemin Tian - , RWTH Aachen University (Author)
  • Anna Reska - , RWTH Aachen University (Author)
  • Björn H Falkenburger - , RWTH Aachen University (Author)
  • Stefan Gründer - , RWTH Aachen University (Author)


Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. They contribute to synaptic transmission, neuronal differentiation and neurodegeneration. ASICs have been mainly characterized in neurons from mice or rats and our knowledge of their properties in human neurons is scarce. Here, we functionally characterized ASICs in differentiating LUHMES cells, a human mesencephalic cell line with characteristics of dopaminergic neurons. We find that LUHMES cells express functional ASICs, predominantly homomeric ASIC1a. Expression starts early during differentiation with a striking surge in current amplitude at days 4-6 of differentiation, a time point where-based on published data-LUHMES cells start expressing synaptic markers. Peak ASIC expression therefore coincides with a critical period of LUHMES cell differentiation. It was associated with increased excitability, but not paralleled by an increase in ASIC1 mRNA or protein. In differentiating as well as in terminally differentiated LUHMES cells, ASIC activation by slight acidification elicited large currents, action potentials and a rise in cytosolic Ca2+. Applying the ASIC pore blocker diminazene during differentiation reduced the length of neurites, consistent with the hypothesis that ASICs play a critical role in LUHMES cell differentiation. In summary, our study establishes LUHMES cells as a valuable model to study the role of ASICs for neuronal differentiation and potentially also cell death in a human cell line.


Original languageEnglish
Article number668008
JournalFrontiers in cellular neuroscience
Publication statusPublished - 2021
Externally publishedYes

External IDs

PubMedCentral PMC8110905
Scopus 85105654455
ORCID /0000-0002-2387-526X/work/150328960