MECHANISMS OF VISUAL TRANSDUCTION

Project: Research project

Project Details

Description

Phototransduction is the process by which light is converted into
electrical signals in the rod and cone cells of the retina. The process
may be conceptually divided into two phases: activation, the sequence of
events leading from light absorption to the diminution of the current
flowing into rods and cones in the dark, and inactivation, the events that
restore the dark resting state. In the past few years a molecular theory
of phototransduction, the cyclic GMP cascade theory, has been formulated
based upon the combined evidence of electrophysiology and biochemistry.
According to this theory, the protein rhodopsin absorbs a photon of light,
and serially activates many G-proteins by catalyzing the binding of the
nucleotide GTP to them; activated G-protein in turns activates
phosphodiesterase, an enzyme that catalyzes the hydrolysis of the internal
messenger, cyclic GMP; a decline in the concentration of free cGMP in the
rod cytoplasm causes the closure of the cGMP-gated cation channel in the
rod plasma membrane, and diminution in the dark current. Although this
molecular theory provides a good qualitative account of activation, a
number of key quantitative issues concerning the activation process remain
unresolved; moreover, many substantive issues remain unresolved about the
molecular mechanisms of inactivation. The proposed research will combine
electrophysiological investigations of isolated amphibian rods, and
biochemical assays of rod membranes of the same species, and will address
several of these unresolved quantitative problems in activation, including
(1) the catalytic rate of G-protein activation by individual rhodopsin
molecules; (2) the stoichiometric relationship between G-protein activation
and phosphodiesterase activation; (3) the enzymatic power of the activated
phosphodiesterase in situ; (4) the quantitative relationship between the
in situ activity of phosphodiesterase and the fraction of the
cGMP-activated channels that remain open. The proposed research will also
investigate the nature and rates of the mechanisms that inactivate
rhodopsin, G-protein, and phosphodiesterase in situ. Theoretical analyses
will try to link the biochemical measurements and the electrophysiological
data in a biophysically rigorous model of the cGMP cascade theory.
StatusFinished
Effective start/end date8/1/788/31/16

Funding

  • National Institutes of Health: $350,562.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $571,356.00
  • National Institutes of Health: $515,502.00
  • National Institutes of Health: $591,737.00
  • National Institutes of Health
  • National Institutes of Health: $526,022.00
  • National Institutes of Health: $576,826.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $189,000.00
  • National Institutes of Health: $566,688.00
  • National Institutes of Health: $591,899.00
  • National Institutes of Health: $204,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $1,112,033.00
  • National Institutes of Health
  • National Institutes of Health: $499,721.00
  • National Institutes of Health: $598,971.00
  • National Institutes of Health: $515,503.00
  • National Institutes of Health
  • National Institutes of Health: $524,600.00
  • National Institutes of Health: $556,883.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $591,678.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $605,471.00

ASJC

  • Medicine(all)

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