All-trans-retinal shuts down rod cyclic nucleotide-gated ion channels: A novel role for photoreceptor retinoids in the response to bright light?
- Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912
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Edited by John E. Dowling, Harvard University, Cambridge, MA, and approved April 11, 2002 (received for review December 8, 2001)
Abstract
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.
Footnotes
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↵* To whom reprint requests should be addressed. E-mail: anita_zimmerman{at}brown.edu.
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This paper was submitted directly (Track II) to the PNAS office.
Abbreviation
- CNG,
- cyclic nucleotide-gated
- Received December 8, 2001.
- Copyright © 2002, The National Academy of Sciences
