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Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cellsRecent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.
Document ID
20040173186
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Leinders-Zufall, T.
(Yale University School of Medicine New Haven, Connecticut 06510, United States)
Shepherd, G. M.
Zufall, F.
Date Acquired
August 22, 2013
Publication Date
June 22, 1996
Publication Information
Publication: Proceedings of the Royal Society of London. Series B. Biological sciences
Volume: 263
Issue: 1371
ISSN: 0962-8452
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: ROL DC 00086
CONTRACT_GRANT: ROL DC 02227
CONTRACT_GRANT: ROL-MH52550
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Neuroscience
Non-NASA Center

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