Ca2+-activated Cl− channel TMEM16A/ANO1 identified in zebrafish skeletal muscle is crucial for action potential acceleration

Dayal, Anamika; Ng, Shu Fun Josephine; Grabner, Manfred

doi:10.1038/s41467-018-07918-z

Cited by 28 publications

(18 citation statements)

References 64 publications

(112 reference statements)

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“…Our data provide explanation of outward rectification previously observed in wholecell recordings of CaCCs [50]. Both the conductance and the open probability of CaCCs increased at positive potentials (Figure 1).…”

Section: Discussionsupporting

confidence: 87%

Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

Kolesnikov

Perevoznikova

Gusev

et al. 2021

IJMS

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Microdomains formed by proteins of endoplasmic reticulum and plasma membrane play a key role in store-operated Ca2+ entry (SOCE). Ca2+ release through inositol 1,4,5-trisphosphate receptor (IP3R) and subsequent Ca2+ store depletion activate STIM (stromal interaction molecules) proteins, sensors of intraluminal Ca2+, which, in turn, open the Orai channels in plasma membrane. Downstream to this process could be activated TRPC (transient receptor potential-canonical) calcium permeable channels. Using single channel patch-clamp technique we found that a local Ca2+ entry through TRPC1 channels activated endogenous Ca2+-activated chloride channels (CaCCs) with properties similar to Anoctamin6 (TMEM16F). Our data suggest that their outward rectification is based on the dependence from membrane potential of both the channel conductance and the channel activity: (1) The conductance of active CaCCs highly depends on the transmembrane potential (from 3 pS at negative potentials till 60 pS at positive potentials); (2) their activity (NPo) is enhanced with increasing Ca2+ concentration and/or transmembrane potential, conversely lowering of intracellular Ca2+ concentration reduced the open state dwell time; (3) CaCC amplitude is only slightly increased by intracellular Ca2+ concentration. Experiments with Ca2+ buffering by EGTA or BAPTA suggest close local arrangement of functional CaCCs and TRPC1 channels. It is supposed that Ca2+-activated chloride channels are involved in Ca2+ entry microdomains.

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Section: Discussionsupporting

confidence: 87%

Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

Kolesnikov

Perevoznikova

Gusev

et al. 2021

IJMS

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“…Rapid activation of TMEM16A can regulate the electrical activity by inducing membrane depolarization or by accelerating action potential repolarization; this has been shown in neurons from dorsal root ganglia, cholinergic neurons of the medial habenula and muscle cells 36,47 . Thus, activation of TMEM16A enables neurons to respond to thermal stimulus, control anxiety-related behaviour 36,47 and increase the frequency of action potentials in skeletal muscle cells of zebrafish 48 . A more direct physiological role for TMEM16A regulation by protons is suggested by its simultaneous activation with H + ATPase in the apical membrane of proximal tubules of mouse kidney 49 .…”

Section: Discussionmentioning

confidence: 99%

Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A)

Segura-Covarrubias

Aréchiga-Figueroa

Jesús-Pérez

et al. 2020

Sci Rep

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Anoctamin-1 (ANO1 or TMEM16A) is a homo-dimeric Ca 2+-activated cl − channel responsible for essential physiological processes. each monomer harbours a pore and a ca 2+-binding pocket; the voltage-dependent binding of two intracellular ca 2+ ions to the pocket gates the pore. However, in the absence of intracellular ca 2+ voltage activates TMEM16A by an unknown mechanism. Here we show voltage-activated anion currents that are outwardly rectifying, time-independent with fast or absent tail currents that are inhibited by tannic and anthracene-9-carboxylic acids. Since intracellular protons compete with ca 2+ for binding sites in the pocket, we hypothesized that voltage-dependent titration of these sites would induce gating. Indeed intracellular acidification enabled activation of TMEM16A by voltage-dependent protonation, which enhanced the open probability of the channel. Mutating Glu/ Asp residues in the ca 2+-binding pocket to glutamine (to resemble a permanent protonated Glu) yielded channels that were easier to activate at physiological pH. notably, the response of these mutants to intracellular acidification was diminished and became voltage-independent. Thus, voltage-dependent protonation of glutamate/aspartate residues (Glu/Asp) located in the Ca 2+-binding pocket underlines TMEM16A activation in the absence of intracellular Ca 2+. Anoctamin-1 (ANO1 or TMEM16A) and Anoctamin-2 (ANO2 or TMEM16B) are the pore-forming subunits of Ca 2+-activated Cl − channels (CaCCs) 1-3. Several tissues express CaCCs that participate in vital physiological functions 4,5. Thus, a role for TMEM16A and TMEM16B in smooth muscle contraction, control of blood pressure, control of gastrointestinal movements, regulation of cardiac and neuronal excitability, fluid secretion in exocrine glands, secretion of melatonin, mucin and insulin, sperm capacitation and motility, inhibition of polyspermy, and sensory transduction was established using tissue-specific knockout mice 6-16. In addition, TMEM16A modulates the partitioning of membrane phosphoinositides and endocytic transport by controlling the [Cl − ] i 17. Overexpression of TMEM16A is associated with hypertension, increased cell proliferation and cancer progression 18-21. Activation of CaCCs is triggered by voltage-dependent binding of two Ca 2+ ions to the channel when the intracellular Ca 2+ concentration ([Ca 2+ ] i) increases 22-26. Structural and mutagenesis analysis show that Ca 2+ ions bind to an acidic Ca 2+ pocket formed by four Glu, one Asp and one Asn 25-27. The pocket is located near the cytosolic side facing the permeation pathway. However, other divalent cations and maybe trivalent cations too can support TMEM16A activation. Based on the cation concentrations to obtain the half-maximum response, the cation selectivity of TMEM16A gating machinery is Ca 2+ »Sr 2+ »Ba 2+ »Cd 2+ , 23,27-29. Gd 3+ may also activate TMEM16A since its application removed the inward rectification of the Gly644Pro TMEM16A mutant channel 30 .

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“…In our current hypoxia study, two orthologs are found-CLCA1 and CLCA3. Recent studies demonstrated that CLCA1 forms non-covalent oligomers in colonic mucus and has Mucin 2-processing properties, playing an important role in regulating the structural arrangement of the mucus and thereby partly mediating mucus processing (Dayal et al, 2019;Nyström et al, 2019). Few reports are available on the functional analysis of CLCA3.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis During the Seven Developmental Stages of Channel Catfish (Ictalurus punctatus) and Tra Catfish (Pangasianodon hypophthalmus) Provides Novel Insights for Terrestrial Adaptation

Shang

et al. 2021

Front. Genet.

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Tra catfish (Pangasianodon hypophthalmus), also known as striped catfish, is a facultative air-breather that uses its swim bladder as an air-breathing organ (ABO). A related species in the same order (Siluriformes), channel catfish (Ictalurus punctatus), does not possess an ABO and thus cannot breathe in the air. Tra and channel catfish serve as great comparative models for investigating possible genetic underpinnings of aquatic to land transitions, as well as for understanding genes that are crucial for the development of the swim bladder and the function of air-breathing in tra catfish. In this study, hypoxia challenge and microtomy experiments collectively revealed critical time points for the development of the air-breathing function and swim bladder in tra catfish. Seven developmental stages in tra catfish were selected for RNA-seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated, and a total of 21,448 unique genes were detected. A comparative genomic analysis between channel catfish and tra catfish revealed 76 genes that were present in tra catfish, but absent from channel catfish. In order to further narrow down the list of these candidate genes, gene expression analysis was performed for these tra catfish-specific genes. Fourteen genes were inferred to be important for air-breathing. Of these, HRG, GRP, and CX3CL1 were identified to be the most likely genes related to air-breathing ability in tra catfish. This study provides a foundational data resource for functional genomic studies in air-breathing function in tra catfish and sheds light on the adaptation of aquatic organisms to the terrestrial environment.

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Ca2+-activated Cl− channel TMEM16A/ANO1 identified in zebrafish skeletal muscle is crucial for action potential acceleration

Cited by 28 publications

References 64 publications

Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A)

Comparative Transcriptome Analysis During the Seven Developmental Stages of Channel Catfish (Ictalurus punctatus) and Tra Catfish (Pangasianodon hypophthalmus) Provides Novel Insights for Terrestrial Adaptation

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