Estimating the rate constant of cyclic GMP hydrolysis by activated phosphodiesterase in photoreceptors

  • Reingruber J
  • Holcman D
  • 16

    Readers

    Mendeley users who have this article in their library.
  • 6

    Citations

    Citations of this article.

Abstract

The early steps of light response occur in the outer segment of rod and cone photoreceptor. They involve the hydrolysis of cGMP, a soluble cyclic nucleotide, that gates ionic channels located in the outer segment membrane. We shall study here the rate by which cGMP is hydrolyzed by activated phosphodiesterase (PDE). This process has been characterized experimentally by two different rate constants beta(d) and beta(sub): beta(d) accounts for the effect of all spontaneously active PDE in the outer segment, and beta(sub) characterizes cGMP hydrolysis induced by a single light-activated PDE. So far, no attempt has been made to derive the experimental values of beta(d) and beta(sub) from a theoretical model, which is the goal of this work. Using a model of diffusion in the confined rod geometry, we derive analytical expressions for beta(d) and beta(sub) by calculating the flux of cGMP molecules to an activated PDE site. We obtain the dependency of these rate constants as a function of the outer segment geometry, the PDE activation and deactivation rates and the aqueous cGMP diffusion constant. Our formulas show good agreement with experimental measurements. Finally, we use our derivation to model the time course of the cGMP concentration in a transversally well-stirred outer segment.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Jürgen Reingruber

  • David Holcman

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free