Ida Mann Lecture. Transduction in human photoreceptors.

Phototransduction (the process by which light triggers a neural response in retinal rod and cone photoreceptors) is now understood at a molecular level. Indeed, the G-protein cascade of phototransduction is one of the best understood of all biological signalling pathways. The diffusional interactions of the proteins underlying the cascade are described and are briefly analysed. In response to a single activated rhodopsin (R*), formed as a result of a single photon hit, it can be shown that molecules of the G-protein will be activated (to G*) at an approximately constant rate. This, in turn, will cause the number of activated molecules of the third protein (the effector protein, E*, a phosphodiesterase) also to rise linearly with time. These kinetics of protein activation lead to an accurate description of the time-course of the rising phase of the photoreceptor's electrical response, both in single-cell recordings and also in recordings of the human electroretinogram (ERG). By analysing the a-wave of the ERG it is possible to determine the 'amplification' of transduction within living photoreceptors, and to begin to localise the molecular site of dysfunction is cases of photoreceptor abnormality.