scholarly journals ASIC3 fine-tunes bladder sensory signaling

2018 ◽  
Vol 315 (4) ◽  
pp. F870-F879 ◽  
Author(s):  
Nicolas Montalbetti ◽  
James G. Rooney ◽  
Allison L. Marciszyn ◽  
Marcelo D. Carattino
Keyword(s):  
Sensory Neurons ◽  
Bladder Function ◽  
Extracellular Acidification ◽  
Acid Sensing Ion Channels ◽  
Sensory Signaling ◽  
Rate Of Decay ◽  
A Subunit ◽  
And Function ◽  
Kinetics Of

Acid-sensing ion channels (ASICs) are trimeric proton-activated, cation-selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~25% of the bladder sensory neurons harvested from both wild-type (WT) and ASIC3 knockout (KO) mice. The absence of ASIC3 increased the magnitude of the peak evoked by extracellular acidification and reduced the rate of decay of the ASIC-like currents. These findings suggest that ASICs are assembled as heteromers and that the absence of ASIC3 alters the composition of these channels in bladder sensory neurons. Consistent with the notion that ASIC3 serves as a proton sensor, 59% of the bladder sensory neurons harvested from WT, but none from ASIC3 KO mice, fired action potentials in response to extracellular acidification. Studies of bladder function revealed that ASIC3 deletion reduces voiding volume and the pressure required to trigger micturition. In summary, our findings indicate that ASIC3 plays a role in the control of bladder function by modulating the response of afferents to filling.

scholarly journals Role of Axonal Odorant Receptors in Olfactory Topography

2020 ◽  
Vol 15 ◽  
pp. 263310552092341
Author(s):  
Claudia Lodovichi
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Axon Terminal ◽  
Internal Representation ◽  
Dual Role ◽  
Odorant Receptors ◽  
Topographic Map ◽  
And Function ◽  
Guidance Molecule

A unique feature in the organization of the olfactory system is the dual role of the odorant receptors: they detect odors in the nasal epithelium and they play an instructive role in the convergence of olfactory sensory neuron axons in specific loci, ie, glomeruli, in the olfactory bulb. The dual role is corroborated by the expression of the odorant receptors in 2 specific locations of the olfactory sensory neurons: the cilia that protrude in the nostril, where the odorant receptors interact with odors, and the axon terminal, a suitable location for a potential axon guidance molecule. The mechanism of activation and function of the odorant receptors expressed at the axon terminal remained unknown for almost 20 years. A recent study identified the first putative ligand of the axonal odorant receptors, phosphatidylethanolamine-binding protein1, a molecule expressed in the olfactory bulb. The distinctive mechanisms of activation of the odorant receptors expressed at the opposite locations in sensory neurons, by odors, at the cilia, and by molecules expressed in the olfactory bulb, at the axon terminal, explain the dual role of the odorant receptors and link the specificity of odor perception with its internal representation, in the topographic map.

scholarly journals Acid-sensing ion channels in sensory signaling

2020 ◽  
Vol 318 (3) ◽  
pp. F531-F543 ◽  
Author(s):  
Marcelo D. Carattino ◽  
Nicolas Montalbetti
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Genetically Modified ◽  
Physiological Processes ◽  
Acid Sensing Ion Channels ◽  
Genetically Modified Mice ◽  
Sensory Processes

Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.

scholarly journals Conserved His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

2020 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

ABSTRACTAcid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here we extract full-length chicken ASIC1a (cASIC1a) from cell membranes using styrene maleic acid (SMA) copolymer, yielding structures of ASIC1a channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1a that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

scholarly journals MeCP2 Is Required for Normal Development of GABAergic Circuits in the Thalamus

2010 ◽  
Vol 103 (5) ◽  
pp. 2470-2481 ◽  
Author(s):  
Zhong-Wei Zhang ◽  
Joseph D. Zak ◽  
Hong Liu
Keyword(s):  
Neurodevelopmental Disorder ◽  
Brain Slices ◽  
Inhibitory Neurons ◽  
Gene Encoding ◽  
Vertebrate Brain ◽  
Gabaergic Synapses ◽  
And Function ◽  
Kinetics Of ◽  
Whole Cell Recordings

Methyl-CpG binding protein 2 (MeCP2) is highly expressed in neurons in the vertebrate brain, and mutations of the gene encoding MeCP2 cause the neurodevelopmental disorder Rett syndrome. This study examines the role of MeCP2 in the development and function of thalamic GABAergic circuits. Whole cell recordings were carried out in excitatory neurons of the ventrobasal complex (VB) of the thalamus and in inhibitory neurons of the reticular thalamic nucleus (RTN) in acute brain slices from mice aged P6 through P23. At P14–P16, the number of quantal GABAergic events was decreased in VB neurons but increased in RTN neurons of Mecp2-null mice, without any change in the amplitude or kinetics of quantal events. There was no difference between mutant and wild-type mice in paired-pulse ratios of evoked GABAergic responses in the VB or the RTN. On the other hand, unitary responses evoked by minimal stimulation were decreased in the VB but increased in the RTN of mutants. Similar changes in the frequency of quantal events were observed at P21–P23 in both the VB and RTN. At P6, however, quantal GABAergic transmission was altered only in the VB not the RTN. Immunostaining of vesicular GABA transporter showed opposite changes in the number of GABAergic synaptic terminals in the VB and RTN of Mecp2-null mice at P18–P20. The loss of MeCP2 had no significant effect on intrinsic properties of RTN neurons recorded at P15–P17. Our findings suggest that MeCP2 differentially regulates the development of GABAergic synapses in excitatory and inhibitory neurons in the thalamus.

scholarly journals The role of β2 integrin in dendritic cell migration during infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tarfa Altorki ◽  
Werner Muller ◽  
Andrew Brass ◽  
Sheena Cruickshank
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Leukocyte Adhesion ◽  
Trichuris Muris ◽  
Dendritic Cell Migration ◽  
And Function ◽  
Kinetics Of

Abstract Background Dendritic cells (DCs) play a key role in shaping T cell responses. To do this, DCs must be able to migrate to the site of the infection and the lymph nodes to prime T cells and initiate the appropriate immune response. Integrins such as β2 integrin play a key role in leukocyte adhesion, migration, and cell activation. However, the role of β2 integrin in DC migration and function in the context of infection-induced inflammation in the gut is not well understood. This study looked at the role of β2 integrin in DC migration and function during infection with the nematode worm Trichuris muris. Itgb2tm1Bay mice lacking functional β2 integrin and WT littermate controls were infected with T. muris and the response to infection and kinetics of the DC response was assessed. Results In infection, the lack of functional β2 integrin significantly reduced DC migration to the site of infection but not the lymph nodes. The lack of functional β2 integrin did not negatively impact T cell activation in response to T. muris infection. Conclusions This data suggests that β2 integrins are important in DC recruitment to the infection site potentially impacting the initiation of innate immunity but is dispensible for DC migration to lymph nodes and T cell priming in the context of T. muris infection.

scholarly journals The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

Acid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here, we extract full-length chicken ASIC1 (cASIC1) from cell membranes using styrene maleic acid (SMA) copolymer, elucidating structures of ASIC1 channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1 that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

C34 Role of TRPV3 in urinary bladder function and sensory signaling

2013 ◽  
Vol 12 (4) ◽  
pp. e1142, C34
Author(s):  
M.K. Lam ◽  
T.K. Mann-Gow ◽  
K. Zvarová ◽  
X. Zhen ◽  
M.M. Moran ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Bladder Function ◽  
Sensory Signaling

scholarly journals Impacts of zinc oxide nano and bulk particles on redox-enzymes of the Punica granatum callus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fatma A. Farghaly ◽  
Abeer A. Radi ◽  
Fatma A. Al-Kahtany ◽  
Afaf M. Hamada
Keyword(s):  
Punica Granatum ◽  
Redox Enzymes ◽  
Zno Nps ◽  
Activity Of Enzymes ◽  
Zinc And Other Minerals ◽  
Callus Tissues ◽  
And Function ◽  
Kinetics Of ◽  
Excessive Accumulation

AbstractThe structure and function of cellular membranes were sustained by redox-enzymes. We studied the interaction between the oxidative stress caused by excessive accumulation of ZnO-nanoparticles (ZnO-NPs) in plants and the role of redox-enzymes that can alleviate this stress. The crude callus extract from pomegranate, which was treated with 0, 10, and 150 µg mL−1 ZnO-NPs or bulk particles (ZnO-BPs), was applied to study the activity and kinetics of redox-enzymes. The elevated ZnO-NPs, enhanced the lipoxygenase and polyphenol oxidase activity, while the ZnO-BPs did not modify them. The activities of superoxide dismutase, catalase, and phenylalanine ammonia-lyase were induced under ZnO-NPs or BPs treatments, whilst the opposite trend of peroxidase was observed. Ascorbate peroxidase activity increased under ZnO-NPs treatments but decreased under ZnO-BPs. The kinetics activity of enzymes showed changes under different levels of NPs and BPs. Additionally, NPs or BPs treatments reduced the uptake of copper, iron, magnesium, but increased zinc accumulation in callus tissues. Meanwhile, these treatments enhanced the accumulation of manganese ions but did not affect the accumulation of potassium and phosphorous in ZnO-NPs or BPs-stressed calli. Collectively, these results gave a quantitative evaluation of the competition of zinc and other minerals on the carriers, and in addition, they provided a basis for how to control ZnO-NPs or BPs toxicity via redox-enzymes.

scholarly journals Determinants of ion selectivity in ASIC1a- and ASIC2a-containing acid-sensing ion channels

2020 ◽  
Vol 152 (2) ◽  
Author(s):  
Timothy Lynagh ◽  
Emelie Flood ◽  
Céline Boiteux ◽  
Zeshan Pervez Sheikh ◽  
Toby W. Allen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Essential Role ◽  
Ion Selectivity ◽  
Site Directed Mutagenesis ◽  
Ion Permeation ◽  
Extracellular Acidification ◽  
Acid Sensing Ion Channels ◽  
Molecular Determinants ◽  
Energy Simulations

Trimeric acid-sensing ion channels (ASICs) contribute to neuronal signaling by converting extracellular acidification into excitatory sodium currents. Previous work with homomeric ASIC1a implicates conserved leucine (L7′) and consecutive glycine-alanine-serine (GAS belt) residues near the middle, and conserved negatively charged (E18′) residues at the bottom of the pore in ion permeation and/or selectivity. However, a conserved mechanism of ion selectivity throughout the ASIC family has not been established. We therefore explored the molecular determinants of ion selectivity in heteromeric ASIC1a/ASIC2a and homomeric ASIC2a channels using site-directed mutagenesis, electrophysiology, and molecular dynamics free energy simulations. Similar to ASIC1a, E18′ residues create an energetic preference for sodium ions at the lower end of the pore in ASIC2a-containing channels. However, and in contrast to ASIC1a homomers, ion permeation through ASIC2a-containing channels is not determined by L7′ side chains in the upper part of the channel. This may be, in part, due to ASIC2a-specific negatively charged residues (E59 and E62) that lower the energy of ions in the upper pore, thus making the GAS belt more important for selectivity. This is confirmed by experiments showing that the L7′A mutation has no effect in ASIC2a, in contrast to ASIC1a, where it eliminated selectivity. ASIC2a triple mutants eliminating both L7′ and upper charges did not lead to large changes in selectivity, suggesting a different role for L7′ in ASIC2a compared with ASIC1a channels. In contrast, we observed measurable changes in ion selectivity in ASIC2a-containing channels with GAS belt mutations. Our results suggest that ion conduction and selectivity in the upper part of the ASIC pore may differ between subtypes, whereas the essential role of E18′ in ion selectivity is conserved. Furthermore, we demonstrate that heteromeric channels containing mutations in only one of two ASIC subtypes provide a means of functionally testing mutations that render homomeric channels nonfunctional.

scholarly journals Role of Xklp3, a Subunit of the Xenopus Kinesin II Heterotrimeric Complex, in Membrane Transport between the Endoplasmic Reticulum and the Golgi Apparatus

1998 ◽  
Vol 143 (6) ◽  
pp. 1559-1573 ◽  
Author(s):  
Nathalie Le Bot ◽  
Claude Antony ◽  
Jamie White ◽  
Eric Karsenti ◽  
Isabelle Vernos
Keyword(s):  
Golgi Apparatus ◽  
Dominant Negative ◽  
Normal Delivery ◽  
Final Destination ◽  
Golgi Region ◽  
Dominant Negative Form ◽  
A Subunit ◽  
And Function ◽  
State Size

The function of the Golgi apparatus is to modify proteins and lipids synthesized in the ER and sort them to their final destination. The steady-state size and function of the Golgi apparatus is maintained through the recycling of some components back to the ER. Several lines of evidence indicate that the spatial segregation between the ER and the Golgi apparatus as well as trafficking between these two compartments require both microtubules and motors. We have cloned and characterized a new Xenopus kinesin like protein, Xklp3, a subunit of the heterotrimeric Kinesin II. By immunofluorescence it is found in the Golgi region. A more detailed analysis by EM shows that it is associated with a subset of membranes that contain the KDEL receptor and are localized between the ER and Golgi apparatus. An association of Xklp3 with the recycling compartment is further supported by a biochemical analysis and the behavior of Xklp3 in BFA-treated cells. The function of Xklp3 was analyzed by transfecting cells with a dominant-negative form lacking the motor domain. In these cells, the normal delivery of newly synthesized proteins to the Golgi apparatus is blocked. Taken together, these results indicate that Xklp3 is involved in the transport of tubular-vesicular elements between the ER and the Golgi apparatus.

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