The Journal of Neuroscience, 1999, 19:RC19:1-6
RAPID COMMUNICATION
Impaired Odor Adaptation in Olfactory Receptor Neurons after
Inhibition of Ca2+/Calmodulin Kinase II
Trese
Leinders-Zufall1,
Minghong
Ma2, and
Frank
Zufall1
1 Department of Anatomy and Neurobiology and Program in
Neuroscience, University of Maryland, Baltimore, Maryland 21201, and
2 Section of Neurobiology, Yale University, New Haven,
Connecticut 06510
Odor adaptation in vertebrate olfactory receptor neurons (ORNs) is
commonly attributed to feedback modulation caused by
Ca2+ entry through the transduction channels, but it
remains unclear and controversial whether this
Ca2+-mediated adaptation resides in the cAMP-gated
channel alone or whether other molecules of the transduction cascade
are modulated as well. Attenuation of adenylyl cyclase activity by
Ca2+/calmodulin-dependent protein kinase II (CaMKII)
has also been proposed as a mechanism for adaptation. To test this in
intact ORNs, we have compared the properties of adaptation induced by a
sustained (8 sec) or brief (100 msec) odor stimulus. Although adaptation induced by both types of stimuli occurs downstream from the
odor receptors and is Ca2+-dependent, only
adaptation induced by a sustained pulse involves alterations in the
odor response kinetics, consistent with a reduction in the rate of
adenylyl cyclase activation. By disrupting CaMKII to block adenylyl
cyclase attenuation using a specific peptide inhibitor of CaMKII,
autocamtide-2-related inhibitory peptide (AIP), we show that this
reaction is necessary for odor adaptation in vivo. With
CaMKII disrupted, adaptation induced by a sustained stimulus is
significantly impaired: the onset rate of adaptation is decreased by
threefold, and the recovery rate from adaptation is increased by up to
sixfold. In contrast, adaptation induced by a brief odor pulse is
unaffected, demonstrating that the effect of AIP must be highly
specific. The results indicate that CaMKII controls the temporal
response properties of ORNs during odor adaptation. We propose that
CaMKII plays a prominent role in odor perception.
Key words:
olfactory adaptation; salamander; calcium signaling; cyclic nucleotide-gated channels; calcium/calmodulin kinase type II; receptor neurons; adenylyl cyclase
Copyright © 1999 Society for Neuroscience 0270-6474/99/$05.00/0
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