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Raju Rajala, Michael Woodruff, Gordon Fain; Modulation of Mouse Rod cGMP-Gated Channels by Grb14. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2459. doi: https://doi.org/.
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Previous experiments indicated that growth factor receptor-bound protein 14 (Grb14) may modulate rod cyclic guanosine nucleotide (cGMP) gated channels by decreasing channel affinity for cGMP. We tested this hypothesis by recording electrical responses from rods in which the gene for the Grb14 protein had been deleted.
Grb14-/- mice were obtained from Dr. Roger Daly, Garvan Institute of Medical Research, Australia. Suction-electrode recordings were made from single mouse rods by methods previously described (e.g. Chen et al., J. Neurosci. 30:16232-40, 2010).
Rod responses of dark-adapted Grb14-/- mice decayed more rapidly than strain-controlled wild-type (WT) rods (Figure 1) with decreased values of τREC at all light intensities; integration time decreased from 292 ± 20 ms (SE, n=15) in WT to 215 ± 12 ms (17) in Grb14-/- mice. This result is consistent with an increase in channel affinity for cGMP produced by deletion of Grb14. Grb14-/- mouse rods also showed a large and significant decrease in the limiting time constant τD from 171 ± 15 ms (15) in WT to 118 ± 5 ms (17) in Grb14-/- rods. Similar though smaller decreases in both τREC and τD were previously reported from mice whose channels lack the calmodulin binding site (Chen et al., 2010), which should also result in increased channel affinity for cGMP. Although Grb14 was reported to translocate from inner to outer segment in the light (Rajala et al. Biochemistry 48:5563-5572, 2009), we saw no apparent difference in the effect of Grb14 gene deletion on response decay in dark-adapted and bleached or background adapted rods, and light adaption in Grb14-/- rods was essentially the same as in WT.
Our results confirm a role of Grb14 as a modulator of mouse rod cGMP-gated channels in both dark-adapted and light-adapted rods. The physiological role of this modulation remains to be elucidated.
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