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The Journal of Neuroscience, October 15, 1999, 19(20):8799-8807
Modulation of the Light Response by cAMP in
Drosophila Photoreceptors
Sylwester
Chyb1, 2,
Wulf
Hevers3,
Michael
Forte4,
William J.
Wolfgang4,
Zvi
Selinger5, and
Roger C.
Hardie1, 3
Departments of 1 Anatomy, 2 Biochemistry,
and 3 Zoology, Cambridge University, Cambridge CB2 3DY,
United Kingdom, 4 Oregon Health Sciences University, Vollum
Institute, Portland, Oregon 97201, and 5 Department of
Biological Chemistry, Institute of Life Sciences, Hebrew University,
Jerusalem, 91904, Israel
Phototransduction in Drosophila is mediated by a
G-protein-coupled phospholipase C transduction cascade in which each
absorbed photon generates a discrete electrical event, the quantum
bump. In whole-cell voltage-clamp recordings, cAMP, as well as
its nonhydrolyzable and membrane-permeant analogs 8-bromo-cAMP
(8-Br-cAMP) and dibutyryl-cAMP, slowed down the macroscopic light
response by increasing quantum bump latency, without changes in bump
amplitude or duration. In contrast, cGMP or 8-Br-cGMP had no effect on
light response amplitude or kinetics. None of the cyclic nucleotides
activated any channels in the plasma membrane. The effects of cAMP were
mimicked by application of the non-specific phosphodiesterase inhibitor
IBMX and the adenylyl cyclase activator forskolin; zaprinast, a
specific cGMP-phosphodiesterase inhibitor, was ineffective. Bump
latency was also increased by targeted expression of either an
activated Gs subunit, which increased endogenous
adenylyl cyclase activity, or an activated catalytic protein kinase A
(PKA) subunit. The action of IBMX was blocked by pretreatment with the
PKA inhibitor H-89. The effects of cAMP were abolished in mutants of
the ninaC gene, suggesting this nonconventional myosin
as a possible target for PKA-mediated phosphorylation. Dopamine (10 µM) and octopamine (100 µM) mimicked the
effects of cAMP. These results indicate the existence of a G-protein-coupled adenylyl cyclase pathway in Drosophila
photoreceptors, which modulates the phospholipase C-based
phototransduction cascade.
Key words:
phototransduction; neuromodulation; TRP; photoreceptor; dopamine; calcium; cross-talk; adenylyl cyclase; phospholipase C
Copyright © 1999 Society for Neuroscience 0270-6474/99/19208799-09$05.00/0
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