Channel modulation and the mechanism of light adaptation in mouse rods.
Vertebrate photoreceptors are thought to adapt to light by a change in Ca(2+), which is postulated to mediate modulation of (1) excited rhodopsin (Rh*) by Ca(2+)-dependent binding of recoverin, (2) guanylyl cyclase activity via Ca(2+)-dependent GCAP proteins, and (3) cyclic nucleotide-gated channels by binding of Ca(2+)-calmodulin. Previous experiments genetically deleted recoverin and the GCAPs and showed that significant regulation of sensitivity survives removal of (1) and (2). We genetically deleted the channel Ca(2+)-calmodulin binding site in the mouse Mus musculus and found that removal of (3) alters response waveform, but removal of (3) or of (2) and (3) together still leaves much of adaptation intact. These experiments demonstrate that an important additional mechanism is required, which other experiments indicate may be regulation of phosphodiesterase 6 (PDE6). We therefore constructed a kinetic model in which light produces a Ca(2+)-mediated decrease in PDE6 decay rate, with the novel feature that both spontaneously activated and light-activated PDE6 are modulated. This model, together with Ca(2+)-dependent acceleration of guanylyl cyclase, can successfully account for changes in sensitivity and response waveform in background light.
Zilkha Neurogenetic Institute and Department of Cell and Neurobiology, University of Southern California, Los Angeles, California 90089-2821, USA.
Jeannie
J
Chen
Michael L
ML
Woodruff
Tian
T
Wang
Francis A
FA
Concepcion
Daniel
D
Tranchina
Gordon L
GL
Fain
D000221:Adaptation, Ocular / Q000235:genetics / Q000502:physiology*; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*
C529481:Cngb1 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D009419:Nerve Tissue Proteins