Phototransduction mechanism in retinal rods and cones. The Friedenwald Lecture.

V ision begins in the rod and cone receptors of the retina, where light is absorbed and a neural signal is generated. This signal, in the form of an electrical hyperpolarization of the cell membrane, influences second-order visual neurons by modulating the rate of neurotransmitter (glutamate) release from the synaptic terminal of the photoreceptor. This release is high in the dark and is reduced in a graded fashion by light." The response of the postsynaptic neurons to light can be a membrane hyperpolarization or depolarization, depending on whether a particular synapse is sign-preserving or sign-inverting. The overall picture of how light generates a membrane hyperpolarization in rods and cones has been known since the late 1960s. The surface membrane of the photoreceptor outer segment has ion channels— the "light-sensitive" channels—that are open in darkness and are permeable to Na. Driven by its electrochemical gradient, Na steadily enters the outer segment in darkness, constituting a "dark current" that partially depolarizes the cell and maintains a high steady release of neurotransmitter from the synaptic terminal. In the light, absorption of photons by the visual pigment in the outer segment somehow leads to the closure of these cation channels, thus stopping the dark current and resulting in a membrane hyperpolarization (Fig. 1). In rods, the visual pigment is predominantly situated in the membranes of the internalized discs" within the outer segment. Thus, a diffusible cytoplasmic messenger appears necessary to mediate between the light absorption event and the closure of the lightsensitive channels on the surface membrane. In cones, where the disc membranes and the surface membrane are continuous with each other," this