Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.
Ca2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+-permeable ion channels. In olfactory sensory neurons (OSNs), such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and, consequently, reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses.
Song
Yijun
Y
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Cygnar
Katherine D
KD
Sagdullaev
Botir
B
Valley
Matthew
M
Hirsh
Sarah
S
Stephan
Aaron
A
Reisert
Johannes
J
Zhao
Haiqing
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009812:Odorants; D009830:Olfactory Bulb / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D000439:Pentanols / Q000494:pharmacology; D012903:Smell / Q000502:physiology*; D013268:Stimulation, Chemical
D002147:Calmodulin; C529481:Cngb1 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D009419:Nerve Tissue Proteins; D000439:Pentanols; C005716:amyl acetate; D000242:Cyclic AMP; D002118:Calcium