scholarly journals TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium

2019 ◽  
Vol 151 (7) ◽  
pp. 954-966 ◽  
Author(s):  
Tiago Henriques ◽  
Emilio Agostinelli ◽  
Andres Hernandez-Clavijo ◽  
Devendra Kumar Maurya ◽  
Jason R. Rock ◽  
...  
Keyword(s):  
Olfactory Epithelium ◽  
Olfactory System ◽  
Purinergic Receptors ◽  
Ion Selectivity ◽  
Ionic Composition ◽  
Physiological Role ◽  
Apical Surface ◽  
Supporting Cells ◽  
Sustentacular Cells

Glial-like supporting (or sustentacular) cells are important constituents of the olfactory epithelium that are involved in several physiological processes such as production of endocannabinoids, insulin, and ATP and regulation of the ionic composition of the mucus layer that covers the apical surface of the olfactory epithelium. Supporting cells express metabotropic P2Y purinergic receptors that generate ATP-induced Ca2+ signaling through the activation of a PLC-mediated cascade. Recently, we reported that a subpopulation of supporting cells expresses also the Ca2+-activated Cl− channel TMEM16A. Here, we sought to extend our understanding of a possible physiological role of this channel in the olfactory system by asking whether Ca2+ can activate Cl− currents mediated by TMEM16A. We use whole-cell patch-clamp analysis in slices of the olfactory epithelium to measure dose–response relations in the presence of various intracellular Ca2+ concentrations, ion selectivity, and blockage. We find that knockout of TMEM16A abolishes Ca2+-activated Cl− currents, demonstrating that TMEM16A is essential for these currents in supporting cells. Also, by using extracellular ATP as physiological stimuli, we found that the stimulation of purinergic receptors activates a large TMEM16A-dependent Cl− current, indicating a possible role of TMEM16A in ATP-mediated signaling. Altogether, our results establish that TMEM16A-mediated currents are functional in olfactory supporting cells and provide a foundation for future work investigating the precise physiological role of TMEM16A in the olfactory system.

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

Effect of basolateral or apical hyposmolarity on apical maxi K channels of everted rat collecting tubule

1995 ◽  
Vol 268 (4) ◽  
pp. F569-F580 ◽  
Author(s):  
L. C. Stoner ◽  
G. E. Morley
Keyword(s):  
Apical Membrane ◽  
Physiological Role ◽  
Reversal Potential ◽  
K Channel ◽  
Apical Surface ◽  
Open Probability ◽  
Volume Regulatory Decrease ◽  
Collecting Tubules ◽  
High Conductance

We are able to evert and perfuse rat cortical collecting tubules (CCT) at 37 degrees C. Patch-clamp techniques were used to study high-conductance potassium channels (maxi K) on the apical membrane. Under control conditions (150 mM Na+ and 5 mM K+ in pipette and bathing solutions), the slope conductance averaged 109.8 +/- 6.6 pS (12 channels), and reversal potential (expressed as pipette voltage) was +26.3 +/- 2.4 mV. The percent of time the channel spends in the open state and unitary current when voltage was clamped to 0 mV were 1.4 +/- 0.7% and 3.12 +/- 0.42 pA, respectively. In six patches voltage clamped to 0 mV, the isosmotic solution perfused through the everted tubule (basolateral surface) was exchanged for one made 70 mosmol/kgH2O hyposmotic to the control saline. Open probability increased from 0.019 to 0.258, an increase of 0.239 +/- 0.065 (P ' 0.005). In four patches where a maxi K channel was evident, no increase in open probability was observed when a hyposmotic saline was placed on the apical surface. However, when vasopressin was present on the basolateral surface, apical application of hyposmotic saline resulted in a series of bursts of channel activity. The average increase in open probability during bursts was (0.055 +/- 0.017, P < 0.005). We conclude that one function of the maxi K channel located in the apical membrane of the rat CCT may be to release intracellular solute (potassium) during a volume regulatory decrease induced by placing a dilute solution on the basolateral surface or when the apical osmolarity is reduced in the presence of vasopressin. These data are consistent with the hypothesis that the physiological role of the channel is to regulate cell volume during water reabsorption.

scholarly journals Divalent Cation Modulation of Ion Permeation in TMEM16 Proteins

2021 ◽  
Vol 22 (4) ◽  
pp. 2209
Author(s):  
Dung M. Nguyen ◽  
Hwoi Chan Kwon ◽  
Tsung-Yu Chen
Keyword(s):  
Alkaline Earth ◽  
Divalent Cations ◽  
Transmembrane Protein ◽  
Ion Selectivity ◽  
Physiological Role ◽  
Ion Permeation ◽  
Membrane Phospholipids ◽  
Anion Channels ◽  
Head Groups

Intracellular divalent cations control the molecular function of transmembrane protein 16 (TMEM16) family members. Both anion channels (such as TMEM16A) and phospholipid scramblases (such as TMEM16F) in this family are activated by intracellular Ca2+ in the low µM range. In addition, intracellular Ca2+ or Co2+ at mM concentrations have been shown to further potentiate the saturated Ca2+-activated current of TMEM16A. In this study, we found that all alkaline earth divalent cations in mM concentrations can generate similar potentiation effects in TMEM16A when applied intracellularly, and that manipulations thought to deplete membrane phospholipids weaken the effect. In comparison, mM concentrations of divalent cations minimally potentiate the current of TMEM16F but significantly change its cation/anion selectivity. We suggest that divalent cations may increase local concentrations of permeant ions via a change in pore electrostatic potential, possibly acting through phospholipid head groups in or near the pore. Monovalent cations appear to exert a similar effect, although with a much lower affinity. Our findings resolve controversies regarding the ion selectivity of TMEM16 proteins. The physiological role of this mechanism, however, remains elusive because of the nearly constant high cation concentrations in cytosols.

Chloride and potassium channel function in alveolar epithelial cells

2003 ◽  
Vol 284 (5) ◽  
pp. L689-L700 ◽  
Author(s):  
Scott M. O'Grady ◽  
So Yeong Lee
Keyword(s):  
Epithelial Cells ◽  
Fluid Layer ◽  
Ionic Composition ◽  
Basolateral Membrane ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Apical Surface ◽  
Alveolar Cell ◽  
Alveolar Epithelial

Electrolyte transport across the adult alveolar epithelium plays an important role in maintaining a thin fluid layer along the apical surface of the alveolus that facilitates gas exchange across the epithelium. Most of the work published on the transport properties of alveolar epithelial cells has focused on the mechanisms and regulation of Na+ transport and, in particular, the role of amiloride-sensitive Na+ channels in the apical membrane and the Na+-K+-ATPase located in the basolateral membrane. Less is known about the identity and role of Cl− and K+ channels in alveolar epithelial cells, but studies are revealing important functions for these channels in regulation of alveolar fluid volume and ionic composition. The purpose of this review is to examine previous work published on Cl− and K+ channels in alveolar epithelial cells and to discuss the conclusions and speculations regarding their role in alveolar cell transport function.

scholarly journals The Role of ACE2 Receptors of the Olfactory System in Anosmia in COVID-19: An Overview

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Mohammad Javad Nasr ◽  
Ali Alizadeh Khatir ◽  
Arefeh Babazadeh ◽  
Soheil Ebrahimpour
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Severe Acute Respiratory Syndrome ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Complete Loss ◽  
Loss Of Consciousness ◽  
Wide Range ◽  
The Central Nervous System

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). The latest data show that more than 211.7 million people were infected and more than 4.4 million deaths have been reported. The illness presents a wide range of symptoms, ranging from mild to severe. Mild symptoms include cough, fever, dyspnea, fatigue, myalgia and arthralgia, anosmia, and dysgeusia. Furthermore, this virus can affect the central nervous system (CNS) and present a range of mild to severe nervous symptoms, from headache and dysphoria to loss of consciousness, coma, paralysis, and acute cerebrovascular disease. The virus can enter nonneuronal cells of the olfactory epithelium and cause a complete loss of smell. Anosmia and hyposmia are commonly reported in clinics, and being asymptomatic or showing mild symptoms can be primary symptoms in early infected persons. Dysgeusia/hypogeusia is another symptom presented with anosmia/hyposmia. In this article, we reviewed the articles of anosmia and suggested a possible mechanism for this.

Substantia nigra osmoregulation: taurine and ATP involvement

2007 ◽  
Vol 292 (5) ◽  
pp. C1934-C1941 ◽  
Author(s):  
Ingrid Morales ◽  
Jose G. Dopico ◽  
Magdalena Sabate ◽  
Tomas Gonzalez-Hernandez ◽  
Manuel Rodriguez
Keyword(s):  
Substantia Nigra ◽  
Purinergic Receptors ◽  
Opposite Effect ◽  
Physiological Role ◽  
Disulfonic Acid ◽  
Microdialysis Probe ◽  
Inhibitory Neurotransmitter ◽  
Taurine Concentration ◽  
Dose Dependent

An extracellular nonsynaptic taurine pool of glial origin was recently reported in the substantia nigra (SN). There is previous evidence showing taurine as an inhibitory neurotransmitter in the SN, but the physiological role of this nonsynaptic pool of taurine has not been explored. By using microdialysis methods, we studied the action of local osmolarity on the nonsynaptic taurine pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent way, a response that was counteracted by compensating osmolarity with choline. The opposite effect (taurine decrease) was observed when osmolarity was increased. Under basal conditions, the blockade of either the AMPA-kainate glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the purinergic receptors with pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid modified the taurine concentration, suggesting that both receptors modulate the extrasynaptic pool of taurine. In addition, these drugs decreased the taurine response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic receptors in the taurine response to osmolarity. The participation of purinergic receptors was also supported by the fact that ATP (which, under basal conditions, increased the extrasynaptic taurine in a dose-dependent way) administered in doses saturating purinergic receptors also decreased the taurine response to hypoosmolarity. Taken together, present data suggest osmoregulation as a role of the nonsynaptic taurine pool of the SN, a function that also involves glutamate and ATP and that could influence the nigral cell vulnerability in Parkinson's disease.

Electrical Coupling in Sustentacular Cells of the Mouse Olfactory Epithelium

2005 ◽  
Vol 94 (2) ◽  
pp. 1001-1012 ◽  
Author(s):  
Fivos Vogalis ◽  
Colleen C. Hegg ◽  
Mary T. Lucero
Keyword(s):  
Gap Junctions ◽  
Olfactory Epithelium ◽  
Electrical Coupling ◽  
Functional Coupling ◽  
Apical Surface ◽  
Pipette Solution ◽  
Whole Cell ◽  
Sustentacular Cells ◽  
Morphological Studies ◽  
Junctional Communication

Sustentacular cells (SCs) line the apical surface of the olfactory epithelium (OE) and provide trophic, metabolic, and mechanical support for olfactory receptor neurons. Morphological studies have suggested that SCs possess gap junctions, although physiological evidence for gap junctional communication in mammalian SCs is lacking. In the present study we investigated whether coupling exists between SCs situated in tissue slices of OE from neonatal (P0–P4) mice. Using whole cell and cell-attached patch recordings from SCs, we demonstrate that SCs are electrically coupled by junctional resistances on the order of 300 MΩ. Under whole cell recording conditions, Alexa 488 added to the pipette solution failed to reveal dye coupling between SCs. Electrical coupling was deduced from the biexponential decay of capacitive currents recorded from SCs and from the bell-shaped voltage dependency of a P2Y-receptor–activated current, both of which were abolished by 18β-glycyrrhetinic acid (20–50 μM), a blocker of gap junctions. These data provide strong evidence for functional coupling between SCs, the physiological importance of which is discussed.

The Role of the Interaction between Fe(III) and Cell Surface in the Accumulation of 67Ga by Tumor Cells

1991 ◽  
Vol 30 (06) ◽  
pp. 290-293 ◽  
Author(s):  
P. Maleki ◽  
A. Martinezi ◽  
M. C. Crone-Escanye ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Ionic Composition ◽  
Iron Complex ◽  
Iron Binding ◽  
Complex Time ◽  
Interaction Product ◽  
Thermodynamic Constant ◽  
Number Of Cells

The study of the interaction between complexed iron and tumor cells in the presence of 67Ga-citrate indicates that a phenomenon of iron-binding related to the thermodynamic constant of stability of the iron complex, and a hydrolysis (or anion penetration) of the interaction product determine the uptake of 67Ga. The effects of various parameters such as ionic composition of the medium, nature of the iron complex, time of incubation and number of cells are discussed.

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