Olfactory CNG Channel Desensitization by Ca2+/CaM via the B1b Subunit Affects Response Termination but Not Sensitivity to Recurring Stimulation

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.

Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons

“…In vertebrate OSNs, several mechanisms have been proposed, including the desensitization of transduction channels, phosphorylation of odorant receptors, inhibition of adenylyl cyclase, and potentiation of phosphodiesterase activity (37,38,45). Recent molecular genetic studies have revealed, however, that adaptation in vertebrate OSNs is more complex than previously understood (46,47). To date, the odor transduction mechanism in Drosophila OSNs remains unclear, although heterologous studies have suggested novel and controversial mechanisms (43).…”

Elevated Cytosolic Cl−Concentrations in Dendritic Knobs of Mouse Vomeronasal Sensory Neurons

“…Both mouse ) and hamster (Liman 2003) VSNs express a Ca 2+ -activated nonselective cation current that might boost sensory signals. By contrast, Ca 2+ /calmodulin mediates VSN adaptation and gain control by inhibition of TRPC2 ), analogous to effective inhibition of cyclic nucleotide-gated channels in sensory neurons of the main olfactory epithelium (Bradley et al 2001(Bradley et al , 2004Munger et al 2001;Song et al 2008).…”

Scaffolding by MUPP1 regulates odorant-mediated signaling in olfactory sensory neurons

“…Mislocalization of the Ca 2+ -binding factor calmodulin, which together with Ca 2+ renders the CNG channel less sensitive to cAMP (Song et al, 2008), could lead to slowed adaptation of the response during sustained odorant exposure. Calmodulin has also been shown to modulate channel properties by activating calmodulin kinases through direct interaction with the Drosophila melanogaster PDZ protein InaD (Chevesich et al, 1997;Xu et al, 1998), and MUPP1 has been shown to bind to the calmodulin-dependent kinase CaMKII (Ackermann et al, 2009).…”