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Activation kinetics and amplification of the phototransduction G-protein cascade revealed in the a wave of the human electroretinogram

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Abstract

A theoretical model1,2 of the phototransduction G-protein cascade predicts that the activation phase of normalized rod responses to brief flashes can be characterized by a parameter, A, the amplification constant. A has the units s-2 (per photoisomerization), and is expressible in terms of biophysical parameters of the cascade. Empirical investigation of amphibian rods has confirmed a number of quantitative predictions of this model1,2, and yielded the estimate A ≈ 0.1 s-2. We have applied the G-protein cascade model to the a-wave of the human ERG, established to be proportional to the receptor photocurrents. The model provides an excellent description of families of a-waves from normal observers, and yields the estimate A ≈ 10 s-2, about 100-fold higher than A of amphibian rods. Theory shows that 25-fold of the 100-fold increase in A is due to the 25-fold smaller volume of the human rod; the residual 4-fold likely due to temperature-dependent increases in the rates of two cascade steps. We show that estimation of A in eyes having photoreceptor disease shows can yield insight into the mechanism of the disease.

© 1993 Optical Society of America

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