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Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels
Matthew C Trudeau1, William N Zagotta
1Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Washington Medical School, Seattle, Washington 98195, USA.
Abstract:
Cyclic nucleotide-gated (CNG) ion channels mediate sensory transduction in olfactory sensory neurons and retinal photoreceptor cells. In these systems, internal calcium/calmodulin (Ca2+/CaM) inhibits CNG channels, thereby having a putative role in sensory adaptation. Functional differences in Ca2+/CaM-dependent inhibition depend on the different subunit composition of olfactory and rod CNG channels. Recent evidence shows that three subunit types (CNGA2, CNGA4, and CNGB1b) make up native olfactory CNG channels and account for the fast inhibition of native channels by Ca2+/CaM. In contrast, two subunit types (CNGA1 and CNGB1) appear sufficient to mirror the native properties of rod CNG channels, including the inhibition by Ca2+/CaM. Within CNG channel tetramers, specific subunit interactions also mediate Ca2+/CaM-dependent inhibition. In olfactory CNGA2 channels, Ca2+/CaM binds to an N-terminal region and disrupts an interaction between the N- and C-terminal regions, causing inhibition. Ca2+/CaM also binds the N-terminal region of CNGB1 subunits and disrupts an intersubunit, N- and C-terminal interaction between CNGB1 and CNGA1 subunits in rod channels. However, the precise N- and C-terminal regions that form these interactions in olfactory channels are different from those in rod channels. Here, we will review recent advances in understanding the subunit composition and the mechanisms and roles for Ca2+/CaM-dependent inhibition in olfactory and rod CNG channels.
Insights
Calcium/calmodulin inhibits cyclic nucleotide-gated (CNG) channels in sensory neurons. Differences in subunit composition between olfactory and rod CNG channels explain functional variations in this inhibition mechanism.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- Cyclic nucleotide-gated (CNG) ion channels are crucial for sensory transduction in olfactory and retinal cells.
- Internal calcium/calmodulin (Ca2+/CaM) inhibits CNG channels, playing a role in sensory adaptation.
- Functional differences in Ca2+/CaM inhibition are linked to distinct subunit compositions of olfactory and rod CNG channels.
Purpose of the Study:
- To review recent advances in understanding the subunit composition of olfactory and rod CNG channels.
- To elucidate the mechanisms of Ca2+/CaM-dependent inhibition in these channels.
- To explore the roles of Ca2+/CaM inhibition in sensory adaptation.
Main Methods:
- Analysis of existing research on CNG channel subunit composition.
- Review of studies investigating Ca2+/CaM binding sites and interactions.
- Comparison of inhibition mechanisms in olfactory versus rod CNG channels.
Main Results:
- Native olfactory CNG channels comprise CNGA2, CNGA4, and CNGB1b subunits, mediating fast Ca2+/CaM inhibition.
- Rod CNG channels, composed of CNGA1 and CNGB1 subunits, exhibit Ca2+/CaM inhibition.
- Ca2+/CaM binds N-terminal regions in both channel types, disrupting specific N- and C-terminal interactions, though the precise regions differ.
Conclusions:
- Subunit composition dictates Ca2+/CaM inhibition in CNG channels.
- Distinct N- and C-terminal interactions mediate Ca2+/CaM-dependent inhibition in olfactory and rod channels.
- Understanding these mechanisms provides insight into sensory adaptation processes.