<i>Clcn2</i>encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands

Romanenko, Victor G.; Nakamoto, Tetsuji; Catalán, Marcelo A.; González-Begné, Mireya; Schwartz, George J.; Jaramillo, Yasna; Sepúlveda, Francisco V.; Figueroa, Carlos D.; Melvin, James E.

doi:10.1152/ajpgi.90384.2008

Cited by 29 publications

(32 citation statements)

References 46 publications

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“…Ex vivo saliva secretion rates were measured in response to IPR in SMGs lacking ClC-2 channel (Clcn2 −/− ) and in WT glands treated with DCPIB and NPPB, two blockers of VRAC. IPR-induced saliva secretion was not affected in Clcn2 −/− glands, supporting previous reports that ClC-2 channels do not play a major role in saliva secretion (22,35). In contrast, IPR-induced saliva secretion was severely decreased by both DCPIB and NPPB.…”

Section: Discussionsupporting

confidence: 87%

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Catalán

Kondo

Peña-Münzenmayer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Activation of an apical Ca 2+ -activated Cl − channel (CaCC) triggers the secretion of saliva. It was previously demonstrated that CaCCmediated Cl − current and Cl − efflux are absent in the acinar cells of systemic Tmem16A (Tmem16A Cl − channel) null mice, but salivation was not assessed in fully developed glands because Tmem16A null mice die within a few days after birth. To test the role of Tmem16A in adult salivary glands, we generated conditional knockout mice lacking Tmem16A in acinar cells (Tmem16A −/− ). Ca 2+ -dependent salivation was abolished in Tmem16A −/− mice, demonstrating that Tmem16A is obligatory for Ca 2+ -mediated fluid secretion. However, the amount of saliva secreted by Tmem16A −/− mice in response to the β-adrenergic receptor agonist isoproterenol (IPR) was comparable to that seen in controls, indicating that Tmem16A does not significantly contribute to cAMP-induced secretion. Furthermore, IPR-stimulated secretion was unaffected in mice lacking Cftr (Cftr ΔF508/ΔF508 ) or ClC-2 (Clcn2 −/− ) Cl − channels. The time course for activation of IPR-stimulated fluid secretion closely correlated with that of the IPR-induced cell volume increase, suggesting that acinar swelling may activate a volume-sensitive Cl − channel. Indeed, Cl − channel blockers abolished fluid secretion, indicating that Cl − channel activity is critical for IPR-stimulated secretion. These data suggest that β-adrenergic-induced, cAMP-dependent fluid secretion involves a volume-regulated anion channel. In summary, our results using acinar-specific Tmem16A −/− mice identify Tmem16A as the Cl − channel essential for muscarinic, Ca 2+ -dependent fluid secretion in adult mouse salivary glands.acinar cell | secretion | Cl − channel | Tmem16A/Ano1 | Cftr channel

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Section: Discussionsupporting

confidence: 87%

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Catalán

Kondo

Peña-Münzenmayer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Immunolocalization-Immunostaining was performed essentially as described previously (37). Briefly, endogenous biotin was blocked using an Avidin/Biotin blocking kit (Vector Laboratories, Burlingame, CA).…”

Section: Heterologous Expression Of Mousementioning

confidence: 99%

“…After biotin blocking, sections stained for LacZ as above were incubated overnight with a rabbit anti-peptide polyclonal antibody (1:500 dilution) directed to a 17-amino acid sequence in the cytoplasmic region of rat AQP5 (Calbiochem). For Tmem16A immunolocalization, submandibular glands from 2-to 3-day-old and 2-to 3-month-old adult mice were fixed with Bouin's fixative and paraffin-embedded (37). Sections were incubated overnight with a rabbit anti-peptide polyclonal antibody (1:1000 dilution) directed to an amino acid sequence (residues 451-466; KDHPRAEYEARVLEKS) flanked by putative transmembrane domains 2 and 3 in the mouse Tmem16A protein (AbFrontier Co., Seoul, Korea).…”

Section: Heterologous Expression Of Mousementioning

confidence: 99%

“…Crude plasma membranes from submandibular salivary glands from C57BL/6 and Best2 Ϫ/Ϫ mice were isolated as before (37). Minced glands were suspended in 1 ml of ice-cold homogenizing buffer containing 250 mM sucrose (J. T. Baker Inc.), 10 mM triethanolamine, 1 g/ml leupeptin, and 0.1 mg/ml phenylmethylsulfonyl fluoride.…”

Section: Heterologous Expression Of Mousementioning

confidence: 99%

“…Voltage clamp experiments were next performed using the standard whole-cell patch clamp technique to test for CaCClike current in single submandibular granular duct cells, which are easily distinguishable from acinar cells by means of their distinctive morphology (37). Identical experimental conditions as in Fig.…”

Section: Best2 Expression In the Duct Cells Of Mouse Submandibular Samentioning

confidence: 99%

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Tmem16A Encodes the Ca2+-activated Cl− Channel in Mouse Submandibular Salivary Gland Acinar Cells

Romanenko

Catalán

Brown

et al. 2010

Journal of Biological Chemistry

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182

199

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Sexual dimorphisms in the transcriptomes of murine salivary glands

et al. 2019

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Transcriptional profiling identified 933 sexually dimorphic genes out of the 14 371 protein‐coding genes expressed in the three major murine salivary glands: parotid, sublingual, and submandibular. Most (89%) sex‐specific genes were enriched in a single gland, while only 0.5% of the sexually dimorphic genes were enriched in all glands. The sublingual gland displayed a strong male sex bias (94% of sex‐enriched genes), while a sex preference was not obvious in the parotid or submandibular glands. A subset of transcription factor genes was correlated with the expression of gland‐specific, sex‐enriched genes. Higher expression of Cftr chloride and Scnn1 sodium channels in the male submandibular correlated with greater NaCl reabsorption. In conclusion, adult salivary glands display sex‐ and gland‐specific differences in gene expression that reflect their unique functional properties.

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Clcn2encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands

Abstract: . Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands.

Cited by 29 publications

References 46 publications

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Tmem16A Encodes the Ca2+-activated Cl− Channel in Mouse Submandibular Salivary Gland Acinar Cells

Sexual dimorphisms in the transcriptomes of murine salivary glands

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