Transmembrane channel-like 4 is involved in pH and temperature-dependent modulation of salty taste

2021 ◽  
Author(s):  
Yoichi Kasahara ◽  
Masataka Narukawa ◽  
Shinji Kanda ◽  
Makoto Tominaga ◽  
Keiko Abe ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Molecular Mechanisms ◽  
Temperature Dependent ◽  
Salt Taste ◽  
Transmembrane Channel ◽  
Salty Taste ◽  
Voltage Dependent ◽  
Taste Reception ◽  
Sensory Evaluations

Abstract Human susceptibility to NaCl varies depending on temperature and pH, the molecular mechanisms of which remain unclear. The voltage-dependent chloride channel, transmembrane channel-like 4 (TMC4), is activated at approximately 40 °C and is suppressed at pH 5.5. As these are similar in character to human sensory evaluations, hTMC4 may be involved in human salt taste reception.

scholarly journals TMC4 is a novel chloride channel involved in high-concentration salt taste sensation

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yoichi Kasahara ◽  
Masataka Narukawa ◽  
Yoshiro Ishimaru ◽  
Shinji Kanda ◽  
Chie Umatani ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Anion Channel ◽  
Chloride Ions ◽  
Glossopharyngeal Nerve ◽  
Molecular Entity ◽  
Taste Sensation ◽  
High Concentration ◽  
Transmembrane Channel ◽  
Voltage Dependent ◽  
Anion Channel Blocker

Abstract“Salty taste” sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl− receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl− channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl−. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.

Association between Hsp90 and the ClC-2 chloride channel upregulates channel function

2006 ◽  
Vol 290 (1) ◽  
pp. C45-C56 ◽  
Author(s):  
Alexandre Hinzpeter ◽  
Joanna Lipecka ◽  
Franck Brouillard ◽  
Maryvonne Baudoin-Legros ◽  
Michal Dadlez ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Fluid Transport ◽  
Cell Swelling ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Mass Spectrometry Identification ◽  
Voltage Dependent ◽  
Channel Expression ◽  
Associated Proteins ◽  
Cellular Stresses

The voltage-dependent ClC-2 chloride channel has been implicated in a variety of physiological functions, including fluid transport across specific epithelia. ClC-2 is activated by hyperpolarization, weakly acidic external pH, intracellular Cl−, and cell swelling. To add more insight into the mechanisms involved in ClC-2 regulation, we searched for associated proteins that may influence ClC-2 activity. With the use of immunoprecipitation of ClC-2 from human embryonic kidney-293 cells stably expressing the channel, followed by electrophoretic separation of coimmunoprecipitated proteins and mass spectrometry identification, Hsp70 and Hsp90 were unmasked as possible ClC-2 interacting partners. Association of Hsp90 with ClC-2 was confirmed in mouse brain. Inhibition of Hsp90 by two specific inhibitors, geldanamycin or radicicol, did not affect total amounts of ClC-2 but did reduce plasma membrane channel abundance. Functional experiments using the whole cell configuration of the patch-clamp technique showed that inhibition of Hsp90 reduced ClC-2 current amplitude and impaired the intracellular Cl− concentration [Cl−]-dependent rightward shift of the fractional conductance. Geldanamycin and radicicol increased both the slow and fast activation time constants in a chloride-dependent manner. Heat shock treatment had the opposite effect. These results indicate that association of Hsp90 with ClC-2 results in greater channel activity due to increased cell surface channel expression, facilitation of channel opening, and enhanced channel sensitivity to intracellular [Cl−]. This association may have important pathophysiological consequences, enabling increased ClC-2 activity in response to cellular stresses such as elevated temperature, ischemia, or oxidative reagents.

Pharmacological mechanism of topiramate in the prophylaxis and treatment of migraine: a review

2018 ◽  
pp. 190-195
Author(s):  
Emanuela Paz Rosas ◽  
Raisa Ferreira Costa ◽  
Silvania Tavares Paz ◽  
Ana Paula Fernandes da Silva ◽  
Manuela Freitas Lyra de Freitas
Keyword(s):  
Cortical Spreading Depression ◽  
Molecular Mechanisms ◽  
Spreading Depression ◽  
Neuronal Excitability ◽  
Mechanisms Of Action ◽  
World Population ◽  
Gamma Aminobutyric Acid ◽  
Pharmacological Mechanism ◽  
Calcium Ion Channels ◽  
Voltage Dependent

Objective: This review sought to bring evidence of studies addressing the mechanisms of action of topiramate in the prevention and treatment of migraine. Background: Migraine is a neurovascular disorder that affects a large part of the world population. The use of prophylactics contributes to the decrease in the frequency and severity of this disease. Among the antiepileptic drugs, the topiramate, has proven to be the most effective for the treatment of migraine. Although the mechanism of action of this drug is still not well elucidated in the literature, there are several molecular mechanisms proposed. Methodology: A survey was carried out in the literature, from February to March 2018, in different databases, using the descriptors: topiramate, migraine and mechanisms of action. After a careful selection, 25 manuscripts were chosen for this review. Results: Evidence from a number of studies has indicated that the main mechanisms of action of topiramate are related to the modulation of voltage-dependent sodium and calcium ion channels, blockade of excitatory glutamate transmission and inhibition by gamma-aminobutyric acid receptors (GABA), AMPA/kainate and some isoenzymes of carbonic anhydrase. In addition, topiramate is involved in the suppression of cortical spreading depression, besides influencing trigeminovascular activity, and neuronal excitability. Conclusion: Thus, topiramate could be involved in the prevention of major events of the pathophysiology of migraine. Acting directly on cortical spreading depression (DAC), trigeminovascular signals and decreased central sensitization of migraine pain.

scholarly journals Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+current in mouse heart by cell volume changes

2005 ◽  
Vol 568 (2) ◽  
pp. 423-443 ◽  
Author(s):  
Guan-Lei Wang ◽  
Ge-Xin Wang ◽  
Shintaro Yamamoto ◽  
Linda Ye ◽  
Heather Baxter ◽  
...  
Keyword(s):  
Cell Volume ◽  
Molecular Mechanisms ◽  
Mouse Heart ◽  
Volume Changes ◽  
Voltage Dependent ◽  
K Current

scholarly journals Ca2+-independent but voltage-dependent quantal catecholamine secretion (CiVDS) in the mammalian sympathetic nervous system

2019 ◽  
Vol 116 (40) ◽  
pp. 20201-20209 ◽  
Author(s):  
Rong Huang ◽  
Yuan Wang ◽  
Jie Li ◽  
Xiaohan Jiang ◽  
Yinglin Li ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Molecular Mechanisms ◽  
Catecholamine Release ◽  
Sensory Cells ◽  
Voltage Dependent ◽  
Sympathetic Nervous ◽  
Vesicular Exocytosis ◽  
Adrenal Chromaffin ◽  
Ganglion Neurons

Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz’s Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca2+-dependent secretion at the quantal level and [5] increases Ca2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility.

Molecular Mechanisms of Mechanoreceptor Adaptation

Physiology ◽  
1994 ◽  
Vol 9 (2) ◽  
pp. 53-59
Author(s):  
OP Hamill ◽  
DW, McBride
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Molecular Mechanisms ◽  
Mechanosensitive Channel ◽  
Cell Adaptation ◽  
Stimulus Domain ◽  
Dynamic Sensitivity ◽  
Voltage Dependent ◽  
Channel Currents

Mechanoreceptor adaptation to maintained stimulation serves to maximize dynamic sensitivity over a broad stimulus domain. Mechanosensitive channel currents in hair cells and oocytes show similar voltage-dependent adaptation. However, in the hair cell, adaptation appears dependent on Ca2+ influx, whereas in the oocyte, it is intrinsically voltage sensitive.

scholarly journals Temperature-dependent increase in the calcium sensitivity and acceleration of activation of ANO6 chloride channel variants

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Haiyue Lin ◽  
Ikhyun Jun ◽  
Joo Han Woo ◽  
Min Goo Lee ◽  
Sung Joon Kim ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Calcium Sensitivity ◽  
Temperature Dependent

Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid

1992 ◽  
Vol 262 (5) ◽  
pp. F799-F806 ◽  
Author(s):  
T. Takenaka ◽  
M. Epstein ◽  
H. Forster ◽  
D. W. Landry ◽  
K. Iijima ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Chloride Channels ◽  
Specific Binding ◽  
Fluorescein Isothiocyanate ◽  
Cytosolic Calcium ◽  
Membrane Depolarization ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Afferent Arterioles ◽  
Subsequent Activation

We have recently proposed that the actions of endothelin (ET) are in part mediated by opening of chloride channels (K. Iijima, L. Lin, A. Nasjletti, and M. S. Goligorsky. Am. J. Physiol. 260 (Cell Physiol. 29: C982-C992, 1991). In the present study the ability of a chloride channel inhibitor, an indanyloxyacetic acid (IAA-94), to block ET-induced effects was examined in cultured vascular smooth muscle cells (VSMC) by spectrofluorometry and direct videomicroscopic visualization of the renal microcirculation in isolated perfused hydronephrotic kidneys (IPHK). A fluorescein isothiocyanate (FITC)-labeled IAA-94 analogue showed specific binding to VSMC. IAA-94 (30 microM) neither affected basal cytosolic calcium concentration ([Ca2+]i) in VSMC nor peak response to ET, but it significantly curtailed sustained elevation of [Ca2+]i (half-time recovery was 147 +/- 23 vs. 248 +/- 33 s in control, P less than 0.05). IAA-94 blunted ET-induced membrane depolarization from 24.5 +/- 3.3 to 8.0 +/- 1.8 mV. In IPHK, ET constricted afferent arterioles (AA) by 29 +/- 2% (18.7 +/- 0.8 to 13.2 +/- 0.6 microns, P less than 0.001). Isradipine reversed this ET-induced vasoconstriction. Pretreatment with IAA-94 did not alter AA diameter, but markedly attenuated ET-induced AA constriction (reduction of AA diameters by only 9 +/- 2%, P less than 0.001). The subsequent addition of isradipine (0.1-1 microM) did not further dilate AA. Our data indicate that IAA-94 markedly attenuates AA vasoconstriction elicited by ET and suggest that ET-induced opening of chloride channels, membrane depolarization, and subsequent activation of voltage-dependent calcium channels contribute to the vasoconstrictor mechanisms of this peptide.

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