CGMP in mouse rods: the spatiotemporal dynamics underlying single photon responses.

Owen P Gross,Marie E Burns,Edward N Pugh Jr

doi:10.3389/fnmol.2015.00006

Owen P Gross, Marie E Burns + Show 1 more

Open Access

https://doi.org/10.3389/fnmol.2015.00006

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Abstract

Vertebrate vision begins when retinal photoreceptors transduce photons into electrical signals that are then relayed to other neurons in the eye, and ultimately to the brain. In rod photoreceptors, transduction of single photons is achieved by a well-understood G-protein cascade that modulates cGMP levels, and in turn, cGMP-sensitive inward current. The spatial extent and depth of the decline in cGMP during the single photon response (SPR) have been major issues in phototransduction research since the discovery that single photons elicit substantial and reproducible changes in membrane current. The spatial profile of cGMP decline during the SPR affects signal gain, and thus may contribute to reduction of trial-to-trial fluctuations in the SPR. Here we summarize the general principles of rod phototransduction, emphasizing recent advances in resolving the spatiotemporal dynamics of cGMP during the SPR.

Highlights

STRUCTURAL AND BIOCHEMICAL CONSTRAINTS ON cGMP SIGNALING IN RODSTHE SPATIAL SPREAD OF cGMP SIGNALING IS RESTRICTED BY THE INTRACELLULAR DISKS The nature of the disk stack Phototransduction occurs within a specialized cylindrical subcellular compartment, the outer segment, which is exclusively devoted to absorbing and transducing photons (Figure 1A)
DcG was estimated to be 40 μm2 s−1, remarkably close to the value 36 μm2 s−1 estimated for rodent rods by Holcman and Korenbrot (2004) solely from geometric considerations. While this analysis of the spatial profile of cGMP during the single photon response (SPR) was based on the steady-state SPR amplitudes driven by “rogue” rhodopsins, the analysis provides a rigorous lower bound on the depth of the cGMP profile and an upper bound on the spatial extent
MEMBRANE FLUX TRUMPS INTRACELLULAR DIFFUSION FOR INTRACELLULAR CALCIUM DYNAMICS For mouse rods with normal Ca2+ feedback to cyclase, theoretical calculations suggest that the spatial extent of the fall in calcium concentration largely mirrors that of cGMP (Figure 3A)

Summary

STRUCTURAL AND BIOCHEMICAL CONSTRAINTS ON cGMP SIGNALING IN RODS

THE SPATIAL SPREAD OF cGMP SIGNALING IS RESTRICTED BY THE INTRACELLULAR DISKS The nature of the disk stack Phototransduction occurs within a specialized cylindrical subcellular compartment, the outer segment, which is exclusively devoted to absorbing and transducing photons (Figure 1A). One experimental approach involves using slits or small spots to deliver light stimuli to different locations in the outer segment while recording the membrane current Such experiments have yielded conflicting results, with some authors concluding that during the SPR cGMP falls only slightly from its resting level over a large spatial extent (Hemilä and Reuter, 1981; Field and Rieke, 2002), while others concluded that the change is highly localized (Lamb et al, 1981; Gray-Keller et al, 1999). DcG was estimated to be 40 μm s−1, remarkably close to the value 36 μm s−1 estimated for rodent rods by Holcman and Korenbrot (2004) solely from geometric considerations While this analysis of the spatial profile of cGMP during the SPR was based on the steady-state SPR amplitudes driven by “rogue” rhodopsins, the analysis provides a rigorous lower bound on the depth of the cGMP profile and an upper bound on the spatial extent. The resulting values of the parameters βdark and DcG are valid generally, and are essential for constraining a spatiotemporal model that incorporates the normal lifetimes of R∗ and E∗, as well as the effects of calcium feedback regulation to cGMP synthesis, as discussed

PDE CONTRIBUTES AMPLIFICATION TO THE SPR BUT ALSO SPEEDS

CONFERRED BY COOPERATIVE CHANNEL GATING CNG channel properties

Contribution of cooperative gating to gain

Findings

Balance between cGMP synthesis and hydrolysis