Myosin II activity is required for structural plasticity at the axon initial segment

Eur J Neurosci. 2017 Jul;46(2):1751-1757. doi: 10.1111/ejn.13597. Epub 2017 May 17.


In neurons, axons possess a molecularly defined and highly organised proximal region - the axon initial segment (AIS) - that is a key regulator of both electrical excitability and cellular polarity. Despite existing as a large, dense structure with specialised cytoskeletal architecture, the AIS is surprisingly plastic, with sustained alterations in neuronal activity bringing about significant alterations to its position, length or molecular composition. However, although the upstream activity-dependent signalling pathways that lead to such plasticity have begun to be elucidated, the downstream mechanisms that produce structural changes at the AIS are completely unknown. Here, we use dissociated cultures of rat hippocampus to show that two forms of AIS plasticity in dentate granule cells - long-term relocation, and more rapid shortening - are completely blocked by treatment with blebbistatin, a potent and selective myosin II ATPase inhibitor. These data establish a link between myosin II and AIS function, and suggest that myosin II's primary role at the structure may be to effect activity-dependent morphological alterations.

Keywords: blebbistatin; cell culture; dentate granule cell; hippocampus.

MeSH terms

  • Animals
  • Axon Initial Segment / drug effects
  • Axon Initial Segment / metabolism*
  • Calcineurin / metabolism
  • Cells, Cultured
  • Central Nervous System Agents / pharmacology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / metabolism
  • Endocytosis / drug effects
  • Endocytosis / physiology
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Myosin Type II / antagonists & inhibitors
  • Myosin Type II / metabolism*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats, Wistar


  • Central Nervous System Agents
  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Calcineurin
  • Myosin Type II