How do visual pigments function in phototransduction and adaptation? Visual
pigments of invertebrates had been shown to be remarkably different from
those of vertebrates. Rhodopsin is not bleached (photolysed into the vitamin
A chromophore and the opsin protein). Rather light converts rhodopsin to
a stable metarhodopsin which is reconverted by light to rhodopsin. I inferred
the properties of each receptor's visual pigment from my early electrophysiological
experiments. Curiously, in the fruit fly, maximal conversion of rhodopsin
to metarhodopsin in R1-6 and R7 completely inactivated these receptors until
the rhodopsin was photoregenerated from metarhodopsin. This permitted a
chromatic adaptation approach which proved very useful in conjunction with
the genetic dissection. It also allowed me to determine the properties of
this inactivation and its underlying mechanism, another unique aspect of
invertebrate photoreceptor function, namely the prolonged depolarizing afterpotential
(PDA). Vitamin A deprivation eliminates the light induced inactivation and
PDA mentioned above. This proved to be especially interesting to laboratories
concentrating on adaptation in invertebrate receptors.
Selected early papers on adaptation and vitamin A deprivation:
Harris, W.A., Ready, D.F., Lipson, E.D., Hudspeth, A.J. and Stark, W.S.
Vitamin A deprivation and Drosophila photopigments. Nature, 1977, 266, 648-650.
Stark, W. S. and Zitzmann, W.G. Isolation of adaptation mechanisms and photopigment
spectra by vitamin A deprivation in Drosophila. Journal of Comparative Physiology,
1976, 105, 15-27.
Freeze fracture EM of rhabdomeric
microvilli of vitamin A replete and deprived Drosophila (from Harris et
The original demonstration, from
vitamin A deprivation experiments, that the R1-6 afterpotential (later called
PDA) and the associated R1-6 inactivation depends on visual pigment level
(from Stark and Zitzmann, 1976)
(now at Rutgers) was one of my colleagues at Hopkins. His interest was alcolol
dehydrogenase, and he had a negative mutant. I thought Adh- might not be
able to convert retinol (vitamin A) to retinal (rhodopsin's chromophore),
and I wanted to test their vision. He suggested that we use some vials of
defined medium he had since we could autoclave them to kill any microbes
that might also convert retinol to retinal. The flies were much less sensitive
and lacked the PDA but Adh+ contols were the same. The medium in the vials
was Sang's medium, devoid of retinoids, and that is how my student, Bill
Zitzmann, and I got started on our vitamin A deprivation work in 1976.
The vitamin A deprivation work proved more competitive than I anticipated.
The Stark and Zitzmann (1976) paper (received Sept. 22, 1975) was followed
in a few weeks by Razmjoo and Hamdorf's (1976) paper (received Dec. 24,
1975), and Bill Zitzmann was dumbfounded by that faster turn-around to publication.
Razmjoo and Hamdorf's paper relied heavily on data from Hamdorf's associate
Joachim Schwemer who was away from Bochum to work in Boston. Joachim came
down to talk with me because he had gotten wind of my recent entry into
this field where he had been working for some time. I had the impression
he was worried about being either scooped or left out. Later, when I met
Kurt Hamdorf in Bochum in 1978, he told me that he had been very mad at
me and perhaps other people as well because he thought someone had told
me of his work and that I then raced to beat him to publication. I tried
my best to explain how it was by accident that I stumbled into studies of
vitamin A deprivation and that I was too young to be talking with people
at European meetings.
I doubt that Kurt Hamdorf ever put the resentment behind him, in part because
of another competition. Bill
Harris, in Seymour Benzer's lab at Caltech, offered an interesting collaboration
on the vitamin A work because he had colleagues who could do the freeze-fracture
and spectrophotometry. Jim Hudpeith helped make the exciting discovery that
microvilli in deprived flies were nearly devoid of the P-face particles
that replete flies had. I got wind from a friend that some Europeans had
already obtained a similar result. I said to my colleagues, "Hurry,"
but instead they did a good job and published our work in Nature (1977).
The Europeans actually beat us to the finish line (their "received"
date was 40 days earlier than ours) with a note in Z. Naturforschung (C.
B. Boschek & K Hamdorf, vol 31c, p. 763, 1976), but I later learned
that the more prestigious Nature had rejected their manuscript.
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This page last revised on March 6, 2007