Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca2+/calmodulin kinase II.
Odor adaptation in vertebrate olfactory receptor neurons (ORNs) is commonly attributed to feedback modulation caused by Ca(2+) entry through the transduction channels, but it remains unclear and controversial whether this Ca(2+)-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 Ca(2+)/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 Ca(2+)-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.
Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland, Baltimore, Maryland 21201, USA.
T
T
Leinders-Zufall
M
M
Ma
F
F
Zufall
D000222:Adaptation, Physiological; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012454:Salamandra; D012903:Smell / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D002118:Calcium