Chloride Accumulation in Mammalian Olfactory Sensory Neurons

Abstract

The generation of an excitatory receptor current in mammalian olfactory sensory neurons (OSNs) involves the sequential activation of two distinct types of ion channels: cAMP-gated Ca 2ϩ -permeable cation channels and Ca

Ca2+-activated Cl− currents are dispensable for olfaction

“…Also, our experiments on isolated OSNs suggest a ~90% contribution of Ano2 to cAMP-induced currents. The disruption of tight junctions during isolation of OSNs may allow ciliary Ano2 channels to spread to the cell body where their electrical accessibility is much better 10 . The length (20-30 µm) and small diameter (0.1 µm) of cilia implies that channels in their distal part contribute little to voltage changes at the cell body, in particular when ciliary membrane conductance is high during signal transduction 44 .…”

“…Taking into account ion concentrations measured in the mucus and the dendritic knob (as surrogate for cilia) 10,14,15 , Cl -gradients across the ciliary membrane should dissipate more easily than those for Na + or Ca 2+ which carry depolarizing currents through CNG channels. Nkcc1 is thought to rapidly replenish ciliary Cl -, which exits through anion channels during signal transduction 10,13 .…”

“…cAMP then opens heteromeric cyclic nucleotide-gated (CNG) cation channels 3 . The resulting influx of Na + and Ca 2+ depolarizes the plasma membrane and raises the cytosolic Ca 2+ concentration ([Ca 2+ ] i ), thereby activating Ca 2+ -activated Cl -channels 1,[4][5][6][7][8][9][10] . All these components of the signal transduction cascade are localized to sensory cilia, which are embedded in the mucus covering the MOE.…”

“…There has been broad consensus that Ca 2+ -activated Cl -channels powerfully amplify olfactory signal transduction 1,[4][5][6][7][8][9][10] . These channels are thought to mediate an outward flow of Cl -, which generates a depolarizing current that, in rodents, is five-to tenfold larger than currents through CNG channels 8,11,12 .…”

“…A prerequisite for Cl -efflux is an inside-out electrochemical Cl --gradient. It is believed that cytosolic chloride concentration of OSNs is raised by the Na + K + 2Cl -co-transporter Nkcc1 9,10,13 and that [Cl -] is low in the mucus surrounding the cilia 14,15 . However, mucosal ion concentrations are difficult to measure in vivo, and Nkcc1 knockout mice display attenuated electro-olfactograms (EOGs) 11,16 , but normal olfactory sensitivity 17 .…”