Developmental expression of retinal cone cGMP-gated channels: Evidence forrapid turnover and trophic regulation

The cyclic GMP-gated cationic channels of vertebrate photo-receptors are es sential for visual phototransduction. We have examined the developmental re gulation of cGMP-gated channels in morphologically identified cones in the chick retina. Expression of cone-type cGMP-gated channel mRNA can be detect ed at embryonic day 6 (E6), but expression of functional channels, as acces sed by patch-clamp recordings, cannot be detected until E8. Plasma membrane channels in embryonic cones have a high turnover rate because inhibition o f protein synthesis or disruption of the Golgi apparatus causes an almost c omplete loss of functional cGMP-gated channels within 12 hr. Different subp opulations of cones begin to express functional channels at different devel opmental stages, but all cones express channels by E10. Expression of cGMP- gated channels in at least one cone subpopulation appears to require one or more soluble differentiation factors, which are presumably present in the normal microenvironment of the developing retina. Application of chick embr yo extract (CEE), a rich source of trophic factors, causes marked stimulati on of cGMP-gated channel expression in chick cones at E8, but not at E6. In hibition of MAP kinase (Erk) signaling using PD98059, or inhibition of PI3 kinase signaling by LY294002, blocked the stimulatory effects of CEE on E8 cones. Several recombinant trophic factors were also tested, but none could mimic the stimulatory effects of CEE on channel expression. In summary, th e developmental expression of cGMP-gated cationic channels in embryonic con es appears to be regulated by epigenetic factors. The ability of cones to r espond to these epigenetic factors is also developmentally regulated.