title: Functional implications of axon initial segment cytoskeletal disruption in stroke.
abstract: 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.
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Stoler
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Fleidervish
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D009473:Neuronal Plasticity; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology
chemical_list: D007473:Ion Channels