1,720,998 research outputs found
Calcium Activated Chloride Channels In Olfactory Transduction
Full text linkCa2+-activated Cl ̄ channels are an important component of olfactory transduction. Odorant binding to odorant receptors in the cilia of olfactory sensory neurons (OSNs) leads to an increase of intraciliary Ca2+ concentration by Ca2+ entry through cyclic nucleotide-gated channels. Ca2+ activates a Cl ̄ channel that leads to an efflux of Cl ̄ from the cilia, contributing to the amplification of the OSN depolarization. The molecular identity of this Cl ̄ channel remains elusive. Recent evidences have indicated that bestrophins are able to form Ca2+-activated Cl ̄ channels channels in heterologous systems. Immunohistochemistry revealed that mBest2 was expressed on the cilia of OSNs, the site of olfactory transduction, and co-localized with the main subunit of cyclic nucleotide-gated channels, CNGA2. We performed a functional comparison of the properties of Ca2+-activated Cl ̄ channels from native channels expressed in dendritic knob/cilia of mouse OSNs with those induced by heterologous expression of mBest2 in HEK-293 cells. Even if the two channels did not display identical characteristics, they have many similar features such as the same anion permeability, the Ca2+ sensitivity in micromolar range and the same side-specific blockage of the two Cl ̄ channel blockers commonly used to inhibit the odorant-induced Ca2+-activated Cl ̄ channels in OSNs, niflumic acid and 4-acetamido-4’-isothiocyanato-stilben-2,2’-disulfonate (SITS). However electroolfactogram recording from mBest2 null mice showed a normal sensitivity to odorant stimulation. Therefore mBest2 is a good candidate for being a molecular component of the olfactory Ca2+-activated Cl ̄ channels but its precise role in olfactory transduction remains to be clarified
Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels.
Full text linkTMEM16A and TMEM16B encode for Ca2+-activated Cl- channels (CaCC) and are expressed in many cell types and play a relevant role in many physiological processes. Here, I performed a site-directed mutagenesis study to understand the molecular mechanisms of ion permeation of TMEM16B. I mutated two positive charged residues R573 and K540, respectively located at the entrance and inside the putative channel pore and I measured the properties of wild-type and mutant TMEM16B channels expressed in HEK-293 cells using whole-cell and excised inside-out patch clamp experiments. I found evidence that R573 and K540 control the ion permeability of TMEM16B depending both on which side of the membrane the ion substitution occurs and on the level of channel activation. Moreover, these residues contribute to control blockage or activation by permeant anions. Finally, R573 mutation abolishes the anomalous mole fraction effect observed in the presence of a permeable anion and it alters the apparent Ca2+-sensitivity of the channel. These findings indicate that residues facing the putative channel pore are responsible both for controlling the ion selectivity and the gating of the channel, providing an initial understanding of molecular mechanism of ion permeation in TMEM16B
Signal Transduction in Vertebrate Olfactory Cilia
No full textComprehensive Overview of Advances in Olfaction The common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely overly simplistic. The Neurobiology of Olfaction provides a thorough analysis of the state-of-the-science in olfactory knowledge and research, reflecting the growing interest in the field. Authors from some of the most respected laboratories in the world explore various aspects of olfaction, including genetics, behavior, olfactory systems, odorant receptors, odor coding, and cortical activity. Until recently, almost all animal research in olfaction was carried out on orthonasal olfaction (inhalation). It is only in recent years, especially in human flavor research, that evidence has begun to be obtained regarding the importance of retronasal olfaction (exhalation). These studies are beginning to demonstrate that retronasal smell plays a large role to play in human behavior. Highlighting common principles among various species - including humans, insects, Xenopus laevis (African frog), and Caenorhabditis elegans (nematodes) - this highly interdisciplinary book contains chapters about the most recent discoveries in odor coding from the olfactory epithelium to cortical centers. It also covers neurogenesis in the olfactory epithelium and olfactory bulb. Each subject-specific chapter is written by a top researcher in the field and provides an extensive list of reviews and original articles for students and scientists interested in further readings
The physiological roles of anoctamin2/TMEM16B and anoctamin1/TMEM16A in chemical senses
Full text linkChemical senses allow animals to detect and discriminate a vast array of molecules. The olfactory system is responsible of the detection of small volatile molecules, while water dissolved molecules are detected by taste buds in the oral cavity. Moreover, many animals respond to signaling molecules such as pheromones and other semiochemicals through the vomeronasal organ. The peripheral organs dedicated to chemical detection convert chemical signals into perceivable information through the employment of diverse receptor types and the activation of multiple ion channels. Two ion channels, TMEM16B, also known as anoctamin2 (ANO2) and TMEM16A, or anoctamin1 (ANO1), encoding for Ca2+−activated Cl ̄ channels, have been recently described playing critical roles in various cell types. This review aims to discuss the main properties of TMEM16A and TMEM16B-mediated currents and their physiological roles in chemical senses. In olfactory sensory neurons, TMEM16B contributes to amplify the odorant response, to modulate firing, response kinetics and adaptation. TMEM16A and TMEM16B shape the pattern of action potentials in vomeronasal sensory neurons increasing the interspike interval. In type I taste bud cells, TMEM16A is activated during paracrine signaling mediated by ATP. This review aims to shed light on the regulation of diverse signaling mechanisms and neuronal excitability mediated by Ca2+−activated Cl ̄ channels, hinting at potential new roles for TMEM16A and TMEM16B in the chemical senses
Paradoxical electro-olfactogram responses in TMEM16B knock-out mice
No full textThe Ca2+-activated Cl over bar channel TMEM16B carries up to 90% of the transduction current evoked by odorant stimulation in olfactory sensory neurons and control the number of action potential firing and therefore the length of the train of action potentials. A loss of function approach revealed that TMEM16B is required for olfactory-driven behaviors such as tracking unfamiliar odors. Here, we used the electro-olfactogram (EOG) technique to investigate the contribution of TMEM16B to odorant transduction in the whole olfactory epithelium. Surprisingly, we found that EOG responses from Tmem16b knock out mice have a bigger amplitude compared to those of wild type. Moreover, the kinetics of EOG responses is faster in absence of TMEM16B, while the ability to adapt to repeated stimulation is altered in knock out mice. The larger EOG responses in Tmem16b knock out may be the results of the removal of the clamping and/or shunting action of the Ca2+-activated Cl over bar currents leading to the paradox of having smaller transduction current but larger generator potential
Odorant Detection and Discrimination in the Olfactory System
No full textThe olfactory system excels in both discrimination and detection of odorants. In mammals, it reliably discriminates more than 3000 structurally diverse odorant molecules and has an amazingly high sensitivity that allows the detection of very low amounts of specific odorant molecules. In addition, the olfactory system has the capability to adapt to ambient odorants, allowing the recognition of a broad range of stimuli. The discrimination among different odorants is achieved by using hundreds of receptors, activated with a combinatorial code. Olfactory transduction uses a canonical second messenger system providing two critical attributes: amplification and high signal-to-noise characteristics, giving the system its remarkable detector capabilities. In this review, we present an introduction to the basic molecular mechanisms of olfactory transduction in olfactory sensory neurons. © 2011 Springer Science+Business Media B.V
Neurobiology of Chemical Communication
No full textThe neurobiological bases of pheromonal communication are introduced by some of the most popular students in the field
The olfactory system: from odorant molecules to perception
No full textThe process leading to olfactory perception begins in the nasal cavity, where odorant molecules reaching the olfactory epithelium bind to a large number of different odorant receptors located in the cilia of olfactory sensory neurons. The number of odorant receptors varies between about 300 in humans and 1200 in mice, representing about 1%-4% of proteins encoded by the entire genome. However, each olfactory sensory neuron expresses only one odorant receptor type that can bind different odorant molecules. Vice versa, each odorant molecule can bind to several odorant receptors according to a unique combinatorial code. Axons of olfactory sensory neurons send information to second-order neurons (mitral and tufted cells) in the olfactory bulb, which in turn project to several cortical areas. Sensory coding in the
Cyclic nucleotide-gated ion channels in sensory transduction
Full text linkAbstractCyclic nucleotide-gated (CNG) channels, directly activated by the binding of cyclic nucleotides, were first discovered in retinal rods, cones and olfactory sensory neurons. In the visual and olfactory systems, CNG channels mediate sensory transduction by conducting cationic currents carried primarily by sodium and calcium ions. In olfactory transduction, calcium in combination with calmodulin exerts a negative feedback on CNG channels that is the main molecular mechanism responsible for fast adaptation in olfactory sensory neurons. Six mammalian CNG channel genes are known and some human visual disorders are caused by mutations in retinal rod or cone CNG genes
- …
