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Does rod phototransduction involve the delayed transition of activated rhodopsin to a second, more active catalytic state?

Published online by Cambridge University Press:  01 November 1998

DAVID R. PEPPERBERG
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago

Abstract

Recovery kinetics of the saturating photocurrent response in amphibian rods suggest regulation of the visual signal by a first-order deactivation reaction with an exponential time constant (τc) of about 2 s. The original hypothesis that τc represents the lifetime of activated rhodopsin (R*) in a single-step deactivation appears at odds with several recent findings, for example, that Ca2+, a known regulator of the enzymatic phosphorylation of R*, does not regulate the value of τc. A recently proposed alternative hypothesis, that τc is the lifetime of activated transducin and that the R* lifetime is relatively short (∼0.4 s), appears consistent with the Ca2+ data but is difficult to reconcile with a high specific catalytic activity of R*. The present theoretical study proposes a rate-equation model of R* activation and deactivation in amphibian rods that is generally consistent with observed properties of the τc-associated reaction and the action of Ca2+ as well as with the stereotyped nature of the single-photon response. The model is developed by considering the effect of background light on a time-dependent variable, Reff*, defined as the effective total level of R* activity. Central starting assumptions are that Ca2+ reduction mediates the effect of background light on Reff*(t) and that background desensitization of the photocurrent flash response derives from this action of Ca2+. Construction of the model is guided by criteria based on previous experimental findings. Among these are the approximate constancy of background desensitization expressed at near-peak and later times in the flash response, and the large (∼10-fold) dynamic range of this desensitization. The proposed model hypothesizes that an event regulated by Ca2+ feedback causes activated rhodopsin to become susceptible to a two-phase, stochastic deactivation process, the second phase of which is characterized by τc. A central prediction of the model is the regulated transition of flash-activated R* to “R**”, a state exhibiting greatly increased catalytic activity.

Type
Research Article
Copyright
1998 Cambridge University Press

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