Cite as:
Hamer R D, Nicholas S C, Tranchina D, Lamb T D, Liebman P A, 2003, "On the reproducibility of rod single-photon responses: The Gordian knot of phototransduction unravelled" Perception 32 ECVP Abstract Supplement

On the reproducibility of rod single-photon responses: The Gordian knot of phototransduction unravelled

R D Hamer, S C Nicholas, D Tranchina, T D Lamb, P A Liebman

At absolute scotopic threshold, individual rods are absorbing photons at intervals of at least several minutes [Rodieck, 1998 The First Steps in Seeing (Sunderland, MA: Sinauer Associates) pp 136 - 137]. Such performance requires single-photon responses (SPRs) reliable enough, and with adequate signal-to-noise ratio for useful visual performance. For the last 25 years, it has been an abiding problem in photoreceptor physiology to reconcile the reproducibility of SPRs with the inherently variable nature of all molecular reactions. In particular, SPRs in vertebrate rods are much less variable than expected if isomerised rhodopsin (R*) inactivated in a single step, and no other variability-reducing mechanisms were available. Several models have been proposed to account for SPR reproducibility, none of which can, alone, account for a broad range of rod dim - flash responses while being based on known biochemistry. We present a new stochastic model of phototransduction ('sequential phosphorylation, or SP model'), the core of which is sequential ratcheting down of R* activity by multiple phosphorylation (Pn) of R*, and a concomitant Pn-dependent increase in the probability of final R* shut-off by arrestin (Arr). We evaluated the model by Monte-Carlo simulations of dim - flash responses, and compared its behaviour with that of a large set of original dim - flash response data (Whitlock and Lamb, 1999 Neuron 23 337 - 351). With 8 steps of R* inactivation (7 Pn steps+Arr), the SP model accounts for observed SPR reproducibility (a prior model hypothesised the need for 10 - 20 steps), and can reproduce key electrophysiological data, including salient features of responses from rods in which R* inactivation was disrupted by genetic manipulation. The evolutionary significance of SPR reproducibility and the 'design' of the mechanisms that support it are discussed.

[Supported by NEI Grant EY115-13, SKERI Fund 5809-0100.]

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