Fluorescence-Based Automated Screening Assay for the Study of the pH-Sensitive Channel ASIC1a

Nausicaa Mazzocchi, Roberta De Ceglia, Davide Mazza, Lia Forti, Luca Muzio, Andrea Domenico Menegon

Research output: Contribution to journalArticlepeer-review

Abstract

Acid-sensing ion channel 1a (ASIC1a) is involved in several pathologies, including neurodegenerative and neuroinflammatory disorders, stroke, epilepsy, and inflammatory pain. ASIC1a has been the subject of intense drug discovery programs devoted to the development of new pharmacological tools for its modulation. However, these efforts to generate new compounds have faced the lack of an efficient screening procedure. In the past decades, improvements in screening technologies and fluorescent sensors for the study of ion channels have provided new opportunities in this field. Unfortunately, ASIC1a is mainly a Na+ permeable channel and undergoes desensitization after its activation, two features that make the use of the available screening procedures problematic. We propose here a novel screening approach for the study of ASIC1a activity in full automation. Our method is based on the stimulation of ASIC1a-expressing cells by protons and the use of electrochromic fluorescent voltage sensors as a readout of ion channel activation. This method will prove to be useful for drug screening programs aimed at ASIC1a modulation.

Original languageEnglish
Pages (from-to)372-380
Number of pages9
JournalJournal of Biomolecular Screening
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • ASIC1a
  • screening
  • voltage sensitive dyes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

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