MYELINATED AXONS AND MOTOR TERMINALS--FUNCTIONAL STUDIES

Project: Research project

Description

The overall goal of the proposed experiments is to learn more about the
dynamic contribution of the internode to the electrical behavior of
myelinated axons, and about mechanisms modulating transmitter release
from motor nerve terminals. Electrophysiological and imaging techniques
will be applied to lizard and rat neuromuscular preparations. Changes in
[Ca2+] and [Na+] within axons and terminals will be measured by injecting
into the axon the Ca-sensitive dye fura- 2 or the Na-sensitive dye SBFI,
and then ratio-imaging fluorescence emissions using an ultra-sensitive
charge-coupled device (CCD) camera. One series of experiments will study
activation of delayed (K) and inward rectifier (Na+K) ion channels in the
internodal (submyelin) axolemma of intact motor axons. We have
demonstrated that internodal delayed rectifier channels are activated
during axonal activity, and will use electrophysiological and imaging
techniques to determine whether the resulting accumulation of K outside
the internodal axolemma increases the likelihood of ectopic discharge, a
mechanism proposed for post-ischemic discharge of human axons in vivo.
Current through inward rectifier channels and electrogenic pump activity
will be detected and localized by measuring post-stimulation changes in
intra-axonal [Na+]. A second series of experiments will study movement of fluorescent dyes
injected into regions of compact myelin. We will use ion- sensitive dyes
to study the cation composition of the dye-filled compartments, both at
rest and following axonal stimulation. We will determine how dye
distribution varies with the charge and size of the injected dye, and in
response to applied currents. These experiments will give new
information concerning myelin sheath permeability. A final series of experiments will measure stimulation-induced changes in
[Ca2+] and [Na+] within motor nerve terminals, along with the correlated
end-plate potentials to measure quantal transmitter release. These
experiments, which include intra-axonal injection of GDP and GTP analogs,
will elucidate mechanisms of hormonal modulation of transmitter release,
and test hypotheses concerning relationships between intracellular
cations and transmitter release. Information gained from these studies may contribute to understanding the
etiology of diseases characterized by dysfunction of myelin (multiple
sclerosis, Guillian-Barre syndrome) or motor nerve terminals.
StatusFinished
Effective start/end date7/1/786/30/09

Funding

  • National Institutes of Health
  • National Institutes of Health: $133,003.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $205,980.00
  • National Institutes of Health
  • National Institutes of Health: $220,248.00
  • National Institutes of Health
  • National Institutes of Health: $273,689.00
  • National Institutes of Health
  • National Institutes of Health: $253,251.00
  • National Institutes of Health: $245,874.00
  • National Institutes of Health: $190,069.00
  • National Institutes of Health: $302,390.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $37,545.00
  • National Institutes of Health: $280,275.00
  • National Institutes of Health
  • National Institutes of Health: $317,820.00

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Axons
Myelin Sheath
Electrophysiology
Mitochondria
Coloring Agents
Lizards
Presynaptic Terminals
Nitric Oxide
Excitatory Postsynaptic Potentials
Action Potentials
Calcium
Vertebrates
Anura
Temperature
Optical Imaging
Chelating Agents
Muscles
Demyelinating Diseases
Patch-Clamp Techniques
Skeletal Muscle

ASJC

  • Medicine(all)
  • Neuroscience(all)