[Frontiers in Bioscience 10, 1191-1204 May 1, 2005]


Xiujun Zhang and Rick H. Cote

Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham, NH 03824-2617, USA


1. Abstract
2. Introduction
3. Metabolic and non-metabolic mechanisms to regulate the cGMP concentration in cells
3.1. Guanylate cyclase (E.C.
3.2. Cyclic nucleotide phosphodiesterase (E.C. and E.C.
3.3. Transport and buffering of cGMP
4. Targets of cGMP action
4.1. cGMP-dependent protein kinase
4.2. Cyclic nucleotide-gated ion channels
4.3. cGMP-binding phosphodiesterases
4.4. Other potential targets of cGMP action
5. Sensory transduction in vertebrate rod and cone photoreceptors
5.1. Rod and cone photoreceptor cells
5.2. Photoreceptor electrophysiology
5.3. Molecular components of visual excitation
5.4. Molecular components of photoresponse termination and adaptation
6. Regulation of cGMP levels in photoreceptors
6.1. cGMP metabolic flux sets the dynamic steady state cGMP concentration
6.2. Buffering and sequestration of cGMP in rod outer segments
7. Targets of cGMP action in photoreceptor cells
7.1. Cyclic nucleotide-dependent protein kinases
7.2. Cyclic nucleotide-gated ion channel
7.3. Photoreceptor PDE6
8. Summary
9. Acknowledgements
10. References


The visual transduction pathway in vertebrate photoreceptors transforms a light stimulus entering the photoreceptor outer segments into an electrical response at the synapses of rod and cone photoreceptor cells. This process is mediated by complex biochemical pathways that precisely regulate cGMP levels, thereby controlling the extent, duration, and adaptation of the photoreceptor to the light stimulus. This review first summarizes the major mechanisms of regulating cytoplasmic cGMP levels (synthesis, degradation, buffering, and efflux) as well as the primary targets of action of cGMP (cyclic nucleotide-gated ion channels, cGMP-dependent protein kinase, and cGMPregulated phosphodiesterases). This information is applied to our current understanding of how these processes operate in the signal-transducing outer segment of rod and cone photoreceptors to carry out visual excitation, recovery, and adaptation in response to light stimulation.