Calcium/Calmodulin Modulation of Olfactory and Rod Cyclic Nucleotide-gated Ion Channels

Matthew C Trudeau,William N Zagotta

doi:10.1074/jbc.r300001200

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.

Highlights

Cyclic nucleotide-gated (CNG)1 ion channels mediate the final step of the enzymatic cascade in sensory cells of the olfactory and visual systems [1,2,3]
In the olfactory system Ca2ϩ ions bind to calmodulin (CaM), and the Ca2ϩ/CaM complex directly inhibits olfactory CNG channels (Fig. 1) [9], constituting a major mechanism underlying olfactory adaptation [7, 10, 11]
In olfactory CNG channels much of the original investigations into mechanism focused on CNGA2 homomeric channels

Summary

Introduction

Cyclic nucleotide-gated (CNG)1 ion channels mediate the final step of the enzymatic cascade in sensory cells of the olfactory and visual systems [1,2,3]. Inhibits native rod CNG channels [13, 14]; the role for Ca2ϩ/CaM in visual adaptation is apparently not as large as in olfactory adaptation [15]. We will focus on recent, intriguing similarities and differences in the molecular mechanisms underlying Ca2ϩ/CaM-dependent inhibition in olfactory and rod CNG channels.

Results

Conclusion