Adaptation memory in photoreceptors: different mechanisms in rods and cones.

Vertebrate rods and cones operate over a wide range of ambient illumination, which is provided by light adaptation mechanisms regulating the sensitivity and speed of the phototransduction cascade. Three calcium-sensitive feedback loops are well established in both rods and cones: acceleration of the quenching of a light-activated visual pigment and cGMP synthesis by guanylate cyclase, and increased affinity of ion channels for cGMP. Accumulating evidence suggests that the molecular mechanisms of light adaptation are more complex. While investigating these putative mechanisms, we discovered a novel phenomenon, observing that the recovery of light sensitivity in rods after turning off non-saturating adaptive light can take tens of seconds. Moreover, after a formal return of the membrane current to the dark level, cell sensitivity to the stimuli remains decreased for a further 1-2 min. We termed this phenomenon of prolonged photoreceptor desensitization 'adaptation memory' (of previous illumination) and the current study is focused on its detailed investigation in rods and an attempt to find the same phenomenon in cones. In rods, we have explored the dependencies of this phenomenon on adapting conditions, specifically, the intensity and duration of adapting illumination. Additionally, we report that fish and frog red-sensitive cones possess similar features of adaptation memory, such as a drop in sensitivity just after the steps of bright light and slow sensitivity recovery. However, we have found that the rate of this process and its nature are not the same as in rods. Our results indicate that the nature of the temporary drop in the sensitivity in rods and cones after adapting steps of light is different. In the rods, adaptation memory could be attributed to the existence of long-lasting modifications of the components of the phototransduction cascade after adapting illumination. In cones, the observed form of the adaptation memory seems to be due to the sensitivity drop caused by a decrease in the availability of the visual pigment, that is, by bleaching.

The effects of dopamine and dopamine receptor agonists on the phototransduction cascade of frog rods.

Purpose: Accumulating evidence suggests that dopamine, the major catecholamine in the vertebrate retina, may modulate cAMP-mediated signaling in photoreceptors to optimize vision in the light/dark cycle. The main putative mechanism of dopamine-induced adaptation changes in photoreceptors is activation of D2-like receptors (D2R), which leads to a decrease of the intracellular cAMP level and reduction of protein kinase A (PKA) activity. However, the mechanisms by which dopamine exerts its regulating effect on the phototransduction cascade remain largely unknown. The aim of the present study was to investigate the effects of dopamine and dopamine receptor agonists on rod photoresponses. Methods: The experiments were performed on solitary rods of the Rana ridibunda frog. Photoreceptor currents were recorded using a suction pipette technique. The effects of dopamine (0.1-50 µM) and selective dopamine receptor agonists-D1R agonist SKF-38393 (0.1-50 µM), D2R agonist quinpirole (2.5-50 µM), and D1-D2 receptor heterodimer agonist SKF-83959 (50 µM)-were examined. Results: We found that, when applied to the rod inner segments (RISs), dopamine and dopamine receptor agonists had no effect on photoresponses. In contrast, the rods responded to dopamine and all agonists applied to their outer segments by decreasing sensitivity to light. At the highest tested concentration (50 µM), the most prominent effect on light sensitivity was induced by D1R agonist SKF-38393, while dopamine, D2R agonist quinpirole, and D1-D2 receptor heterodimer agonist SKF-83959 produced somewhat lower and approximately equal effects. Moreover, SKF-38393 reduced sensitivity at all tested concentrations starting from the smallest one (0.1 µM), whereas dopamine and quinpirole started their action from the higher concentrations of 2.5 µM and 50 µM, respectively. In addition, dopamine, SKF-38393, and quinpirole, on average, did not change the intracellular calcium level as judged from the "exchange current", while SKF-83959 increased it by ~1.3 times. Conclusions: Dopamine induces a decrease in rod sensitivity, mostly by reducing the activation rate of the cascade, and to a much lesser extent, speeding up the turning off of the cascade. The sign of the reaction to all tested drugs, lack of selectivity of dopamine and dopamine receptor agonist action, and analysis of factors that determine sensitivity of photoreceptors suggest that, in rod outer segments (ROSs), dopamine action is mediated by D1-D2 receptor heterodimers but not D1R or D2R alone. This work supports the assumption made earlier by other authors that dopamine exercises its regulatory effect via at least two independent mechanisms, which are cAMP and Ca2+ mediated.

Elevated cAMP improves signal-to-noise ratio in amphibian rod photoreceptors.

The absolute sensitivity of vertebrate retinas is set by a background noise, called dark noise, which originates from several different cell types and is generated by different molecular mechanisms. The major share of dark noise is produced by photoreceptors and consists of two components, discrete and continuous. Discrete noise is generated by spontaneous thermal activations of visual pigment. These events are undistinguishable from real single-photon responses (SPRs) and might be considered an equivalent of the signal. Continuous noise is produced by spontaneous fluctuations of the catalytic activity of the cGMP phosphodiesterase. This masks both SPR and spontaneous SPR-like responses. Circadian rhythms affect photoreceptors, among other systems by periodically increasing intracellular cAMP levels ([cAMP]in), which increases the size and changes the shape of SPRs. Here, we show that forskolin, a tool that increases [cAMP]in, affects the magnitude and frequency spectrum of the continuous and discrete components of dark noise in photoreceptors. By changing both components of rod signaling, the signal and the noise, cAMP is able to increase the photoreceptor signal-to-noise ratio by twofold. We propose that this results in a substantial improvement of signal detection, without compromising noise rejection, at the rod bipolar cell synapse.