ORIGIN OF REPRODUCIBILITY IN THE RESPONSES OF RETINAL RODS TO SINGLE PHOTONS

The single photon responses of retinal rod cells are remarkably reprod ucible, allowing the number and timing of photon absorptions to be enc oded accurately. This reproducibility is surprising because the elemen tary response arises from a single rhodopsin molecule, and typically s ignals from single molecules display large intertrial variations. We h ave investigated the mechanisms that make the rod's elementary: respon se reproducible. Our experiments indicate that reproducibility cannot be explained by saturation within the transduction cascade, by Ca2+ fe edback, or by feedback control of rhodopsin shutoff by any known eleme nt of the cascade; We suggest instead that deactivation through a seri es of previously unidentified transitions allows the catalytic:activit y of a single rhodopsin molecule to decay with low variability. Two ob servations are consistent with this view. First, the time course of rh odopsin's catalytic activity could not be accounted for by the time re quired for the known steps:in rhodopsin deactivation-phosphorylation a nd arrestin binding; Second, the variability of the elementary respons e increased When phosphorylation was made rate-limiting for rhodopsin shutoff.