T. Leinderszufall et al., MODULATION BY CYCLIC-GMP OF THE ODOR SENSITIVITY OF VERTEBRATE OLFACTORY RECEPTOR-CELLS, Proceedings - Royal Society. Biological Sciences, 263(1371), 1996, pp. 803-811
Recent evidence has indicated a significant role for the cGMP second m
essenger system in vertebrate olfactory transduction but no clear func
tions have been identified for cGMP so far. Here, we have examined the
effects of 8-Br-cGMP and carbon monoxide (GO) on odour responses of s
alamander olfactory receptor neurons using perforated patch recordings
. We report that 8-Br-cGMP strongly downregulates the odour sensitivit
y 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 K
1/2 of 1 mu M. Sensitivity modulation is achieved through a regulatory
chain of events in which cGMP stimulates a persistent background curr
ent due to the activation of cyclic nucleotide-gated channels. This in
turn leads to sustained Ca2+ entry providing a negative feedback sign
al. One consequence of the Ca2+ entry is a shift to the right of the s
timulus-response curve and a reduction in saturating odour currents. T
ogether, 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 cGM
P is a marked prolongation of the odour response kinetics. The effects
of CO/cGMP are long-lasting and can continue for minutes. Hence, we p
ropose that cGMP helps to prevent saturation of the cell's response by
adjusting the operational range of the cAMP cascade and contributes t
o olfactory adaptation by decreasing the sensitivity of olfactory rece
ptor cells to repeated odour stimuli.