Dark continuous noise from visual pigment as a major mechanism underlying rod–cone difference in light sensitivity

Retinal rods and cones underlie scotopic and photopic vision, respectively. Their pigments exhibit spontaneous isomerizations (quantal noise) in darkness due to intrinsic thermal energy. This quantal noise, albeit exceedingly low in rods, dictates the light threshold for scotopic vision. The same quantal noise in cones, however, is too low to explain the much higher diurnal light threshold. Separately, a dark continuous noise is present in rods, long accepted to originate from an intrinsic random activation of the cyclic guanosine monophosphate (cGMP)-phosphodiesterase enzyme mediating phototransduction downstream of the pigment. Here, we report the surprising finding that most of this rod dark continuous noise actually originates from rhodopsin itself. Importantly, we found the same continuous noise with a much higher magnitude from cone pigments. The rod and cone continuous noises are apparently both associated with a hitherto unrecognized "metastable" pigment conformational state physiologically resembling that in apo-opsin (opsin devoid of chromophore) and is intermittently active for very brief moments. The cone holopigment's high continuous noise is expected to act as an intrinsic equivalent light and adapt the cone dramatically, accounting for a major part of the light-sensitivity difference between rods and cones in darkness.