Functional implications of axon initial segment cytoskeletal disruption in stroke

Ohad Stoler, Ilya A. Fleidervish

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


Axon initial segment (AIS) is the proximal part of the axon, which is not covered with a myelin sheath and possesses a distinctive, specialized assembly of voltage-gated ion channels and associated proteins. AIS plays critical roles in synaptic integration and action potential generation in central neurons. Recent evidence shows that stroke causes rapid, irreversible calpain-mediated proteolysis of the AIS cytoskeleton of neurons surrounding the ischemic necrotic core. A better understanding of the molecular mechanisms underlying this "non-lethal" neuronal damage might provide new therapeutic strategies for improving stroke outcome. Here, we present a brief overview of the structure and function of the AIS. We then discuss possible mechanisms underlying stroke-induced AIS damage, including the roles of calpains and possible sources of Ca 2+ ions, which are necessary for the activation of calpains. Finally, we discuss the potential functional implications of the loss of the AIS cytoskeleton and ion channel clusters for neuronal excitability.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalActa Pharmacologica Sinica
Issue number1
StatePublished - 1 Jan 2016


  • Ca2+
  • axon initial segment
  • calpain
  • sodium channels
  • spreading depression
  • stroke

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Functional implications of axon initial segment cytoskeletal disruption in stroke'. Together they form a unique fingerprint.

Cite this