All-trans-retinal shuts down rod cyclic nucleotide-gated ion channels: a novel role for photoreceptor retinoids in the response to bright light?
In retinal rods, light-induced isomerization of 11-cis-retinal to all-trans-retinal within rhodopsin triggers an enzyme cascade that lowers the concentration of cGMP. Consequently, cyclic nucleotide-gated (CNG) ion channels close, generating the first electrical response to light. After isomerization, all-trans-retinal dissociates from rhodopsin. We now show that all-trans-retinal directly and markedly inhibits cloned rod CNG channels in excised patches. 11-cis-retinal and all-trans-retinol also inhibited the channels, but at somewhat higher concentrations. Single-channel analysis suggests that all-trans-retinal reduces average open probability of rod CNG channels by inactivating channels for seconds at a time. At physiological cGMP levels, all-trans-retinal inhibited in the nanomolar range. Our results suggest that all-trans-retinal may be a potent regulator of the channel in rods during the response to bright light, when there is a large surge in the concentration of all-trans-retinal.
Dean
Dylan M
DM
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
Nguitragool
Wang
W
Miri
Andrew
A
McCabe
Sarah L
SL
Zimmerman
Anita L
AL
D000818:Animals; D002417:Cattle; D054815:Cyclic Nucleotide-Gated Cation Channels; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008027:Light; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D012172:Retinaldehyde / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology*; D014981:Xenopus
D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D012176:Retinoids; D012172:Retinaldehyde