Activation and desensitization of the olfactory cAMP-gated transduction channel: identification of functional modules

Olfactory receptor neurons respond to odor stimulation with a receptor potential that results from the successive activation of cyclic AMP (cAMP)-gated, Ca(2+)-permeable channels and Ca(2+)-activated chloride channels. The cAMP-gated channels open at micromolar concentrations of their ligand and are...

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Bibliographic Details
Published in:The Journal of general physiology Vol. 134; no. 5; p. 397
Main Authors: Waldeck, Clemens, Vocke, Kerstin, Ungerer, Nicole, Frings, Stephan, Möhrlen, Frank
Format: Journal Article
Language:English
Published: United States 01.11.2009
Subjects:
Calcium - metabolism
Calcium Signaling
Cyclic AMP - metabolism
Cyclic Nucleotide-Gated Cation Channels - genetics
Cyclic Nucleotide-Gated Cation Channels - metabolism
Electrophysiology
Ion Channel Gating
Mutagenesis, Site-Directed
Olfactory Receptor Neurons - metabolism
Protein Subunits - genetics
Protein Subunits - metabolism
ISSN:1540-7748, 1540-7748
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Summary:Olfactory receptor neurons respond to odor stimulation with a receptor potential that results from the successive activation of cyclic AMP (cAMP)-gated, Ca(2+)-permeable channels and Ca(2+)-activated chloride channels. The cAMP-gated channels open at micromolar concentrations of their ligand and are subject to a Ca(2+)-dependent feedback inhibition by calmodulin. Attempts to understand the operation of these channels have been hampered by the fact that the channel protein is composed of three different subunits, CNGA2, CNGA4, and CNGB1b. Here, we explore the individual role that each subunit plays in the gating process. Using site-directed mutagenesis and patch clamp analysis, we identify three functional modules that govern channel operation: a module that opens the channel, a module that stabilizes the open state at low cAMP concentrations, and a module that mediates rapid Ca(2+)-dependent feedback inhibition. Each subunit could be assigned to one of these functions that, together, define the gating logic of the olfactory transduction channel.
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ISSN:1540-7748
1540-7748
DOI:10.1085/jgp.200910296