April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Cone Photocurrent Stability: Role of CNG Ion Channel Modulation
Author Affiliations & Notes
  • Juan I. Korenbrot
    Physiology Department, Univ California - San Francisco, San Francisco, California
  • Footnotes
    Commercial Relationships  Juan I. Korenbrot, None
  • Footnotes
    Support  NIH Grant EY05498, Sandler Foundation at UCSF
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6576. doi:
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      Juan I. Korenbrot; Cone Photocurrent Stability: Role of CNG Ion Channel Modulation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6576.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To determine the physiological role of the well characterized Ca++-dependent modulation of ligand sensitivity in cone photoreceptor cGMP-gated (CNG) ion channels

Methods: : Using tight-seal electrodes in the whole-cell mode, photocurrents were measured in single cones isolated from striped bass retina. Under voltage clamp, photocurrents were measured in response to light flashes, steps and flashes superimposed on steps. A computational model was developed based on the now known biochemical and biophysical events underlying cone phototransduction, including CNG modulation. Model was optimally fit to experimental data using features experimentally known in bass single cones.

Results: : In bass single cone photoreceptors, photocurrents elicited by the various stimuli tested in dark- and light-adapted conditions reproduce the features previously documented by others in different species. Flash photocurrents are rapid, exhibit a small undershoot at the end of recovery and light adaptation accelerates them and reduces their photosensitivity. Step photocurrents exhibit a sag while light remains constant and a small undershoot at light off. Using a single set of parameters, taken from the literature or from experimental findings in bass cones, the newly developed computational model fits well photocurrents elicited by all stimulation protocols in each cell. In the same model, specific omission of CNG channel modulation (computational transgenesis) causes catastrophic failure to fit experimental data. In particular, transgenic simulated photocurrents match photocurrent activation but exhibit large, dampened oscillations in both flash and step responses, enhanced gain and slower speed of response.

Conclusions: : Ca++-dependent modulation of cGMP sensitivity in cone photoreceptor CNG ion channels is critically important to attain the stability and reproducibility characteristic of cone photocurrents. In the absence of modulation, channel reopening would be controlled by cGMP alone resulting in a return to a dark current that would, at first, be larger in amplitude than it starting value. Such dark current enhancement would cause cytoplasmic Ca++ overload and dampened current oscillation. In the presence of modulation, channel reopening is controlled by the rise of both cytoplasmic cGMP and Ca++. Modulation assures channels reopen at an appropriate rate, thus controlling the rate of cytoplasmic Ca++ recovery. This insures stability in a Ca++-dependent negative feedback loop, a potentially unstable control system.

Keywords: photoreceptors • ion channels • calcium 

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