Developmental expression of retinal cone cGMP-gated channels: evidence for rapid turnover and trophic regulation.
The cyclic GMP-gated cationic channels of vertebrate photoreceptors are essential for visual phototransduction. We have examined the developmental regulation of cGMP-gated channels in morphologically identified cones in the chick retina. Expression of cone-type cGMP-gated channel mRNA can be detected at embryonic day 6 (E6), but expression of functional channels, as accessed by patch-clamp recordings, cannot be detected until E8. Plasma membrane channels in embryonic cones have a high turnover rate because inhibition of protein synthesis or disruption of the Golgi apparatus causes an almost complete loss of functional cGMP-gated channels within 12 hr. Different subpopulations of cones begin to express functional channels at different developmental 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 embryo extract (CEE), a rich source of trophic factors, causes marked stimulation of cGMP-gated channel expression in chick cones at E8, but not at E6. Inhibition 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, the developmental expression of cGMP-gated cationic channels in embryonic cones appears to be regulated by epigenetic factors. The ability of cones to respond to these epigenetic factors is also developmentally regulated.
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Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5513, USA.
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D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002457:Cell Extracts / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002867:Chromones / Q000494:pharmacology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System; D009025:Morpholines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism*
D002457:Cell Extracts; D002867:Chromones; D054815:Cyclic Nucleotide-Gated Cation Channels; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007473:Ion Channels; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006152:Cyclic GMP; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one