MOLECULAR MOTION IN NERVE SODIUM CHANNELS

  • Landowne, David, (PI)

Project: Research project

Description

Two optical measurement techniques will be used to study changes in
molecular conformation associated with excitability of nerve cell
membranes. Two nerve preparations will used; isolated olfactory nerves of
garfish and internally perfused and voltage- clamped segments of squid
giant axons. Previous work by the author has linked changes in optical retardation
(birefringence) with molecular motion underlying activation and
inactivation of sodium channels of squid axons. This method is sensitive to
the orientation of molecular dipoles, here the re-orientation of peptide
bonds within the sodium channel molecule is thought to produce the signals.
In many ways this signal is comparable to polarization (gating) currents
studied by others. Various treatments which modify nerve excitability will
be investigated using the birefringence methods. In particular, the effects
of calcium concentration on the birefringence response to voltage changes
will be measured and correlated with the effects on the electrical current
. The second optical measurement is of optical rotation (circular
birefringence). Recently a Japanese worker has reported a change in optical
rotation associated with action potentials in lobster nerves and in squid
axons. This rotation signal had a different time course than the
birefringence signal .Optical rotation senses the chirality of molecules.
The most likely candidate for the signals observed are changes in the
secondary, structure of a protein, for example, a change from alpha-helix
to beta-sheet is a change in the overall chirality of the peptide bonds. In
this project an attempt will be made to repeat the original observations in
gas nerves and squid axons using the original method of modulating the
polarization of the incident light beam and a new method based on a
two-frequency (Zeeman split) laser. The project will then continue to
characterize the rotation signal with internally perfused voltage-clamped
squid axons and use the variety of manipulations developed to test the
association of the birefringence response to see if the rotation response
reflects changes in the sodium channel molecules and its relation to the
birefringence, gating and ionic sodium current responses. Healthy nerves are excitable in a balanced way and alterations of
excitability are seen in disease states and also during treatments such as
anesthesia. This project will provide information at the molecular and
sub-molecular level to allow us to understand excitability and its
variation. There is a long history of the application of the results
obtained on invertebrate nerve cells to vertebrates including humans. In
addition studies of nerve sodium channels have often led to understanding
of other channels in other tissues with potential health relatedness.
StatusFinished
Effective start/end date8/2/907/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health: $85,947.00
  • National Institutes of Health: $88,321.00
  • National Institutes of Health
  • National Institutes of Health: $87,415.00

Fingerprint

Birefringence
Sodium Channels
Axons
Optical Rotation
Decapodiformes
Olfactory Nerve
Invertebrates
Action Potentials
Vertebrates
Lasers
Sodium
Calcium
Neurons
Light
Peptides
Health
Therapeutics
Proteins

ASJC

  • Medicine(all)
  • Neuroscience(all)