The cytoskeletal protein α-actinin regulates acid-sensing ion channel 1a through a C-terminal interaction

Mikael K. Schnizler, Katrin Schnizler, Xiang Ming Zha, Duane D. Hall, John A. Wemmie, Johannes W Hell, Michael J. Welsh

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The acid-sensing ion channel 1a (ASIC1a) is widely expressed in central and peripheral neurons where it generates transient cation currents when extracellular pH falls. ASIC1a confers pH-dependent modulation on postsynaptic dendritic spines and has critical effects in neurological diseases associated with a reduced pH. However, knowledge of the proteins that interact with ASIC1a and influence its function is limited. Here, we show that α-actinin, which links membrane proteins to the actin cytoskeleton, associates with ASIC1a in brain and in cultured cells. The interaction depended on an α-actinin- binding site in the ASIC1a C terminus that was specific for ASIC1a versus other ASICs and for α-actinin-1 and -4. Co-expressing α-actinin-4 altered ASIC1a current density, pH sensitivity, desensitization rate, and recovery from desensitization. Moreover, reducing α-actinin expression altered acid-activated currents in hippocampal neurons. These findings suggest that α-actinins may link ASIC1a to a macromolecular complex in the postsynaptic membrane where it regulates ASIC1a activity.

Original languageEnglish (US)
Pages (from-to)2697-2705
Number of pages9
JournalJournal of Biological Chemistry
Issue number5
StatePublished - Jan 30 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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