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Submyelin potassium accumulation may functionally block subsets of local axons during deep brain stimulation: a modeling study.

Deep brain stimulation has been used for over a decade to relieve the symptoms of Parkinson's disease, although its mechanism of action remains poorly understood. To better understand the direct effects of DBS on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K(+) accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K(+) accumulation in the submyelin space. The functional block occurs for a range of model parameters: high stimulation frequencies (>130 Hz); high extracellular K(+) concentrations (>3 x 10(-3) M); low maximum Na(+)/K(+) ATPase current densities (<0.026 A m(-2)); low diffusion coefficients for K(+) diffusion out of the submyelin space (<2.4 x 10(-9) m(2) s(-1)); small periaxonal space widths of the myelin attachment sections (<2.7 x 10(-9) m) and perinodal/internodal sections (<8.4 x 10(-9) m). These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency.

Pubmed ID: 18566505


  • Bellinger SC
  • Miyazawa G
  • Steinmetz PN


Journal of neural engineering

Publication Data

September 29, 2008

Associated Grants


Mesh Terms

  • Action Potentials
  • Animals
  • Axons
  • Computer Simulation
  • Deep Brain Stimulation
  • Humans
  • Models, Neurological
  • Nerve Fibers, Myelinated
  • Neural Conduction
  • Potassium
  • Ranvier's Nodes