VISUAL TRANSDUCTION IN RETINA 
King-Wai Yau, Ph.D., Investigator 
Dr. Yau's research is focused on the process of vi- 
sual transduction in the retina. Vision begins in the 
retinal rod and cone receptors, where light is ab- 
sorbed and transduced into an electrical signal. 
This signal, consisting of a graded membrane hy- 
perpolarization, is then transmitted to second- 
order visual neurons by way of modulating the 
release of synaptic transmitter from the photo- 
receptor: in darkness the rate of transmitter release 
is high, and in the light this release is reduced in a 
graded fashion by the membrane hyperpolariza- 
tion. Rods and cones, which subserve vision in dim 
and bright light, respectively, differ from each 
other: rods are —100 times more sensitive to light 
than cones. The responses of rods to a flash of light 
also last longer, so that temporal integration is 
more effective, permitting rods to show an even 
higher sensitivity to steps of light. 
In recent years much progress has been made in 
understanding the transduction process in rods. It 
is now known that the light-sensitive conductance, 
the closure of which in the light produces electrical 
hyperpolarization, is kept open in the dark by cyclic 
GMP (cGMP). Light, on the other hand, activates a 
specific phosphodiesterase to reduce the level of 
intracellular cGMI^ thus leading to conductance 
closure. The activation of this phosphodiesterase 
involves photoisomerized rhodopsin and a GTP- 
binding protein. In cones the transduction process 
also seems to be similar qualitatively. Recently, Dr. 
Yau's laboratory has also shown that, in both rods 
and cones, the closure of the light-sensitive con- 
ductance triggers a negative-feedback regulation, 
mediated by a decrease in the intracellular concen- 
tration of free calcium ions, that rapidly reduces the 
gain of the phototransduction process. This feed- 
back appears to play an important role in the well- 
known phenomenon of light adaptation, because 
when the feedback is experimentally removed, the 
photoreceptor cells lose most of their ability to 
adapt to background light. 
During the past year the laboratory has been en- 
gaged in two investigations: 1) examination of the 
adaptation behavior of mammalian rod receptors to 
background light and 2) study of the gating charac- 
teristics of the cation channel that mediates the 
phototransduction process. 
I. Background Adaptation in Mammalian Rods. 
One important attribute of the visual system is 
the property of light adaptation, which allows the 
visual system to maintain the ability to detect con- 
trast, despite large changes in the light level. In 
cold-blooded vertebrates, part of the ability of the 
visual system to adapt to background light resides 
in the rod receptors themselves. In mammals, on 
the other hand, the widespread belief is that the 
rod receptors scarcely adapt at all, leaving the task 
to postreceptor elements. Recently, Dr. Yau and his 
colleagues found that, in cold-blooded vertebrates, 
an important mechanism underlying receptor adap- 
tation comes from a negative feedback mediated by 
intracellular calcium changes. Furthermore, this 
feedback serves an important function in darkness 
by stabilizing the steady ionic current through the 
cGMP-gated conductance and therefore maintain- 
ing the well-being of the cells. Thus the absence of 
background adaptation in mammalian rod recep- 
tors implies the lack of such a calcium feedback, 
which would jeopardize the ion homeostasis in 
these cells in darkness as well. This situation seems 
highly undesirable and unlikely. To settle this ques- 
tion. Dr. Yau and his colleagues undertook a com- 
prehensive study of rod cells from a variety of mam- 
malian species, including rabbit, cattle, cat, rat, and 
several primate species. In all cases the property of 
adaptation to background light was observed, 
much like in rods of lower vertebrates. Thus the 
previous belief of others is proven wrong. 
II. Gating Characteristics of the cGMP-gated 
Channel. 
The cGMP-activated conductance mediating pho- 
totransduction in retinal rods and cones represents 
a member (another member is the ion channel me- 
diating olfactory transduction) of a novel class of 
ion channels that are gated directly by cyclic nucle- 
otides acting as ligands. The details of the gating 
process, in particular the kinetics, however, remain 
unclear for any of these channels. Dr. Yau's group 
has undertaken a detailed study of the cGMP-gated 
conductance in cones by recording the openings 
and closings of single channels from excised 
patches of cone outer segment plasma membrane; 
all divalent cations were removed, because other- 
wise the channels would be blocked and the ampli- 
tude of the open-channel current reduced to a level 
below detection threshold. In addition to studying 
the channel kinetics at low cGMP concentrations, 
they have also examined the dependence of chan- 
Continued 
555 
