RECOVERY KINETICS OF HUMAN ROD PHOTOTRANSDUCTION INFERRED FROM THE 2-BRANCHED A-WAVE SATURATION FUNCTION

Electroretinographic data obtained from human subjects show that brigh t test flashes of increasing intensity induce progressively longer per iods of apparent saturation of the rod-mediated electroretinogram (ERG ) a wave. A prominent feature of the saturation function [the function that relates the saturation period T with the natural logarithm of fl ash intensity (In I-f] is its two-branched character. At relatively lo w flash intensities (I-f below similar to 4 x 10(4) scotopic troland s econd), T increases approximately in proportion to I-f with a slope [D elta T/Delta(ln I-f)] of similar or equal to 0.3 s. At higher flash in tensities, a different Linear relation prevails, in which [Delta T/Del ta(ln I-f)] is similar or equal to 2.3 s [Invest. Ophthalmol. Vis. Sci . 36, 1603 (1995)]. Based on a model for photocurrent recovery in isol ated single rods [Vis. Neurosci. 8, 9 (1992)], it was suggested that t he upper-branch slope of similar or equal to 2.3 s represents tau(R), the lifetime of photoactivated rhodopsin (R). Here we show that a mo dified version of this model provides an explanation for the lower bra nch of the a-wave saturation function. In this model, tau(E) is the e xponential lifetime of an activated species (E) within the transducin or guanosine 3', 5'-cyclic monophosphate (cGMP) phosphodiesterase sta ges of rod phototransduction; the generation of E by a single R* occu rs within temporally defined, elemental domains of disk membrane; and E(x), the immediate product of E deactivation, is converted only slow ly (time constant tau(Ex)) to E, the form susceptible to reactivation by R. The model predicts that the decay of flash-activated cGMP phosp hodiesterase (PDE) is largely independent of the deactivation kinetic s of R at early postflash times (i.e., at times preceding or comparab le with the lifetime tau(E)) and that the lower-branch slope (similar or equal to 0.3 s) of the a-wave saturation function represents tau(E ). The predicted early-stage independence of PDE* decay and R* deacti vation furthermore suggests a basis for the relative constancy of the single-photon response observed in studies of isolated rods. Numerical evaluation of the model yields a value of similar or equal to 6.7 s f or the time constant tau(Ex). (C) 1996 Optical Society of America