DOES ROD PHOTOTRANSDUCTION INVOLVE THE DELAYED TRANSITION OF ACTIVATED RHODOPSIN TO A 2ND, MORE ACTIVE CATALYTIC STATE

Recovery kinetics of the saturating photocurrent response in amphibian rods suggest regulation of the visual signal by a first-order deactiv ation reaction with an exponential time constant (tau(c)) of about 2 s . The original hypothesis that tau(c) represents the lifetime of activ ated 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 t au(c). A recently proposed alternative hypothesis, that tau(c) is the lifetime of activated transducin and that the R lifetime is relativel y short (similar to 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 consis tent with observed properties of the tau(c)-associated reaction and th e action of Ca2+ as well as with the stereotyped nature of the single- photon response. The model is developed by considering the effect of b ackground light on a time-dependent variable, R-eff, defined as the e ffective total level of R activity. Central starting assumptions are that Ca2+ reduction mediates the effect of background light on R-eff( t) and that background desensitization of the photocurrent flash respo nse derives from this action of Ca2+. Construction of the model is gui ded by criteria based on previous experimental findings. Among these a re the approximate constancy of background desensitization expressed a t near-peak and later times in the flash response, and the large (simi lar to 10-fold) dynamic range of this desensitization. The proposed mo del hypothesizes that an event regulated by Ca2+ feedback causes activ ated rhodopsin to become susceptible to a two-phase, stochastic deacti vation process, the second phase of which is characterized by tau(c). A central prediction of the model is the regulated transition of flash -activated R to ''R**'', a state exhibiting greatly increased catalyt ic activity.