Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca2+/Calmodulin kinase II

被引:76
作者
Leinders-Zufall, T
Ma, MH
Zufall, F
机构
[1] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA
[2] Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA
[3] Yale Univ, Sect Neurobiol, New Haven, CT 06510 USA
关键词
olfactory adaptation; salamander; calcium signaling; cyclic nucleotide-gated channels; calcium/calmodulin kinase type II; receptor neurons; adenylyl cyclase;
D O I
10.1523/JNEUROSCI.19-14-j0005.1999
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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+/calmodulindependent 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.
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页数:6
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