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Published on: October 29, 2011
Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not
Yijun Song1, Katherine D Cygnar, Botir Sagdullaev
1Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Abstract:
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.
Insights
Calcium/calmodulin desensitization of olfactory cyclic nucleotide-gated (CNG) channels is crucial for terminating sensory neuron responses, not adaptation to repeated stimuli. This finding impacts our understanding of olfactory signal processing.
Area of Science:
- Neuroscience
- Molecular Biology
- Sensory Physiology
Background:
- Calcium (Ca2+)/calmodulin-mediated negative feedback regulates Ca2+-permeable ion channels.
- This mechanism is believed to be key for olfactory sensory neuron (OSN) adaptation.
- The cyclic nucleotide-gated (CNG) channel in OSNs is a primary target of this regulation.
Purpose of the Study:
- To investigate the role of Ca2+/calmodulin desensitization in olfactory CNG channel function.
- To determine the specific contribution of fast desensitization to OSN adaptation and response termination.
Main Methods:
- Generated a mouse model with a mutation in the CNGB1b subunit of the CNG channel, conferring resistance to Ca2+/calmodulin desensitization.
- Recorded OSN responses to olfactory stimuli in both wild-type and mutant mice.
Main Results:
- Mutant OSNs exhibited normal adaptation to repeated odorant stimulation.
- However, mutant OSNs displayed slower response termination and reduced olfactory information transmission to the olfactory bulb.
- A reduced decline in response during sustained odorant exposure was also observed in mutant OSNs.
Conclusions:
- Fast Ca2+/calmodulin desensitization of olfactory CNG channels plays a minor role in adaptation to recurring stimuli.
- This desensitization mechanism is primarily important for the timely termination of OSN responses.
- The findings necessitate a re-evaluation of the role of CNG channel desensitization in olfactory signal processing.
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