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

Abstract

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) alpha wave. A prominent feature of the saturation function [the function that relates the saturation period T with the natural logarithm of flash intensity (ln I(f)] is its two-branched character. At relatively low flash intensities (I(f) below approximately 4 x 10(4) scotopic troland second), T increases approximately in proportion to ln I(f) with a slope [delta T/delta (ln I(f)] of approximately 0.3 s. At higher flash intensities, a different linear relation prevails, in which [deltaT/delta(ln I(f) is approximately 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 approximately 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 alpha-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 Ex, 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 (approximately 0.3s) of the a-wave saturation function represent 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 approximately 6.7s for the time constant tau Ex.