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

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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) a wave. A prominent feature of the saturation function [the function that relates the saturation period T with the natural logarithm of flash intensity (ln If] is its two-branched character. At relatively low flash intensities (If below ~4 × 104 scotopic troland second), T increases approximately in proportion to ln If with a slope [ΔT/Δ(ln If)] of ≃0.3 s. At higher flash intensities, a different linear relation prevails, in which [ΔT/Δ(ln If)] is ≃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 ≃2.3 s represents τR*, 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, τE* 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 τEx) 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 τE*) and that the lower-branch slope (≃0.3 s) of the a-wave saturation function represents τE*. 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 ≃6.7 s for the time constant τEx