Recovery kinetics of human rod phototransduction inferred from the two-branched a-wave saturation function

Electroretinographic data obtained from human subjects show that bright test flashes of increasing intensity induce progressively longer periods 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 flash intensity (In I-f] is its two-branched character. At relatively low flash intensities (I-f below similar to 4 x 10(4) scotopic troland second), T increases approximately in proportion to I-f with a slope [Delta T/Delta(ln I-f)] of similar or equal to 0.3 s. At higher flash intensities, a different Linear relation prevails, in which [Delta T/Delta(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 isolated single rods [Vis. Neurosci. 8, 9 (1992)], it was suggested that the 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 modified version of this model provides an explanation for the lower branch of the a-wave saturation function. In this model, tau(E)* is the exponential lifetime of an activated species (E*) within the transducin or guanosine 3', 5'-cyclic monophosphate (cGMP) phosphodiesterase stages of rod phototransduction; the generation of E* by a single R* occurs within temporally defined, elemental domains of disk membrane; and E(x), the immediate product of E* deactivation, is converted only slowly (time constant tau(Ex)) to E, the form susceptible to reactivation by R*. The model predicts that the decay of flash-activated cGMP phosphodiesterase (PDE*) is largely independent of the deactivation kinetics of R* at early postflash times (i.e., at times preceding or comparable 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* deactivation 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 for the time constant tau(Ex). (C) 1996 Optical Society of America