The Journal of Neuroscience, January 1, 2001, 21(1):221-229
Developmental Expression of Retinal Cone cGMP-Gated Channels:
Evidence for Rapid Turnover and Trophic Regulation
Gladys Y.-P.
Ko,
Michael L.
Ko, and
Stuart E.
Dryer
Department of Biology and Biochemistry, University of Houston,
Houston, Texas 77204-5513
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.
Key words:
CNG channels; photoreceptor; cone; retina; development; chick embryo
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