Journal article
Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation
The Journal of neuroscience, Vol.35(24), pp.9225-9235
06/17/2015
DOI: 10.1523/JNEUROSCI.3563-14.2015
PMCID: PMC4469743
PMID: 26085644
Abstract
Despite the expression of homologous phototransduction components, the molecular basis for differences in light-evoked responses between rod and cone photoreceptors remains unclear. We examined the role of cGMP phosphodiesterase (PDE6) in this difference by expressing cone PDE6 (PDE6C) in rd1/rd1 rods lacking rod PDE6 (PDE6AB) using transgenic mice. The expression of PDE6C rescues retinal degeneration observed in rd1/rd1 rods. Double-transgenic rods (PDE6C++) were compared with rd1/+ rods based on similar PDE6 expression. PDE6C increased the basal PDE activity and speeded the rate-limiting step for phototransduction deactivation, causing rod photoresponses to appear light adapted, with reduced dark current and sensitivity and faster response kinetics. When PDE6C++ and rd1/+ rods were exposed to similar background light, rd1/+ rods displayed greater desensitization. These results indicate an increased spontaneous activity and faster deactivation of PDE6C compared with PDE6AB in darkness, but that background light increases steady PDE6C activity to a lesser extent. In addition to accelerating the recovery of the photoresponse, faster PDE6C deactivation may blunt the rise in background-induced steady PDE6C activity. Therefore, higher basal PDE6C activity and faster deactivation together partially account for faster and less sensitive cone photoresponses in darkness, whereas a reduced rise of steady PDE6C activity in background light may allow cones to avoid saturation.
Cones are the primary photoreceptors responsible for most of our visual experience. Cone light responses are less sensitive and display speeded responses compared with rods. Despite the fact that rods and cones use a G-protein signaling cascade with similar organization, the mechanistic basis for these differences remains unclear. Here, we examined the role of distinct isoforms of PDE6, the effector enzyme in phototransduction, in these differences. We developed a transgenic mouse model that expresses cone PDE6 in rods and show that the cone PDE6 isoform is partially responsible for the difference in sensitivity and response kinetics between rods and cones.
Details
- Title: Subtitle
- Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation
- Creators
- Anurima Majumder - Department of Molecular Physiology and Biophysics andJohan Pahlberg - Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, California 90095Hakim Muradov - Department of Molecular Physiology and Biophysics andKimberly K Boyd - Department of Molecular Physiology and Biophysics andAlapakkam P Sampath - Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, California 90095 nikolai-artemyev@uiowa.edu asampath@jsei.ucla.eduNikolai O Artemyev - Department of Molecular Physiology and Biophysics and Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa 52242, and nikolai-artemyev@uiowa.edu asampath@jsei.ucla.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.35(24), pp.9225-9235
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.3563-14.2015
- PMID
- 26085644
- PMCID
- PMC4469743
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R01 EY010843 / NEI NIH HHS R01 EY-017606 / NEI NIH HHS R01 EY-010843 / NEI NIH HHS P30 EY000331 / NEI NIH HHS R01 EY017606 / NEI NIH HHS EY-000331 / NEI NIH HHS
- Language
- English
- Date published
- 06/17/2015
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025317102771
Metrics
20 Record Views