ON THE MOLECULAR-ORIGINS OF THERMAL NOISE IN VERTEBRATE AND INVERTEBRATE PHOTORECEPTORS

Retinal photoreceptors generate discrete electrical events in the dark indistinguishable from those evoked by light and the resulting dark s ignals limit visual sensitivity at low levels of illumination. The ran dom spontaneous events are strongly temperature dependent and in both vertebrate and invertebrate photoreceptors require activation energies usually in the range of 23 to 28 kcal mol(-1). Recent molecular orbit al studies and pH experiments on horseshoe crabs (Limulus) suggest tha t the thermal isomerization of a relatively unstable form of rhodopsin , one in which the Schiff-base linkage between the chromophore and pro tein is unprotonated, is responsible for thermal noise. This mechanism is examined in detail and compared to other literature models for pho toreceptor noise. We conclude that this two-step process is likely to be the principal source of noise in all vertebrate and invertebrate ph otoreceptors. This model predicts that the rate of photoreceptor noise will scale in proportion to 10(-xi), where xi is the pK(a) of the Sch iff base proton on the retinyl chromophore. Nature minimizes photorece ptor noise by selecting a binding site geometry which shifts the pK(a) of the Schiff base proton to > 16, a value significantly larger than the pK(a) of the chromophore in bacteriorhodopsin (pK(a) approximate t o 13) or model protonated Schiff bases in solution (pK(a) approximate to 7).