cAMP-Dependent Regulation of the Phototransduction Cascade in Cones

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cAMP-Dependent Regulation of the Phototransduction Cascade in Cones V. S. Sitnikova, L. A. Astakhova, and M. L. Firsov

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 106, No. 4, pp. 448–461, April, 2020. Original article submitted February 19, 2020. Revised version received February 25, 2020. Accepted February 25, 2020. Retinal photoreceptors – cones and rods – are able to undergo light adaptation over a wide range of illumination levels due to a complex of regulatory mechanisms. Among these, the best studied are calcium feedback circuits, which can explain about 50% of the actual regulation of light sensitivity. There are other regulatory mechanisms also able to adjust photoreceptor light responses depending on the illumination level, in particular regulation of the phototransduction cascade through the diurnal rhythm. During the dark phase of the diurnal cycle, cAMP levels in photoreceptors increase and rod sensitivity increases, which can be regarded as an adaptive action. In the case of cones, which operate at high illumination levels and make virtually no contribution to vision in twilight conditions, the increase in sensitivity in the dark phase may not have adaptive value. We report here our studies of how changes in [cAMP]in affect the operation of the phototransduction cascade in carp cones. Increases in [cAMP]in were obtained by incubating cells with the adenylate cyclase activator forskolin. Forskolin was found to slow both phases – the rise phase and the descending phase – of the light response in cones. As a result, cones, in contrast to rods, did not respond to forskolin with increases in light sensitivity but showed an almost two-fold reduction in the dark current. Thus, the reaction of the cone phototransduction cascade to increases in [cAMP]in was significantly different from the reaction in rods. This effect of [cAMP]in in cones may also have adaptive value – not in the form of increased sensitivity but as a reduction in the metabolic load on cells not functioning in the dark phase. Keywords: cone, phototransduction, circadian rhythm, camp, rod.

Photoreceptors in vertebrates are able to adapt over a very wide range of intensities. Adaptation ability is supported by a whole complex of regulatory mechanisms using different mediator systems. Historically, the first and best studied is the group of mechanisms regulated by the intracellular calcium concentration [1–6]. The source of the regulatory action for all these mechanisms is a change in the balance between calcium influx and efflux through the plasma membrane of the outer segment of the photoreceptor. Activation of photoreceptors by light leads to partial or complete opening of cGMP-controlled plasma membrane channels and decreases in or termination of sodium and calcium ion influx into the outer segment, while outward pumping of cal-

cium from the cytosol by means of the Na,K/Ca exchanger continues at the former rate and is independent of the level of activation of photoreceptors by light [7]. The calcium con