Anoctamin 1 (Ano1) is required for glucose-induced membrane potential oscillations and insulin secretion by murine β-cells

Autor: Myrna Virreira, Nicolas Markadieu, Abdullah Sener, Philippe Golstein, Alain Boom, Raphaël Crutzen, Willy Malaisse, Vadim Shlyonsky, Renaud Beauwens
Jazyk: angličtina
Rok vydání: 2015
Předmět:
0301 basic medicine
Physiology
medicine.medical_treatment
Clinical Biochemistry
Chloride Channels -- antagonists & inhibitors -- metabolism
Membrane Potentials
Mice
Physiologie générale
Insulin-Secreting Cells
Insulin
Cells
Cultured
Membrane potential
Médecine clinique [chimie clinique]
biology
Chemistry
Physiologie de la régulation
Chlorides -- metabolism
Chloride channel
Bumetanide
Ion Channels
Receptors and Transporters
medicine.drug
Islet
medicine.medical_specialty
Insulin -- metabolism
Chloride
Exocytosis
ANO1
03 medical and health sciences
Chlorides
Chloride Channels
Physiology (medical)
Internal medicine
medicine
Repolarization
Animals
Humans
Rats
Wistar
Anoctamin-1
TMEM16A
Physiologie générale [animale]
Glucose -- metabolism
Rats
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Membrane repolarization
Glucose
Biophysics
biology.protein
Calcium -- metabolism
Calcium
Insulin-Secreting Cells -- metabolism -- physiology
Zdroj: Pflugers Archiv
Pflügers Archiv, 468 (4
Pflügers Archiv
ISSN: 1432-2013
0031-6768
Popis: Anions such as Cl− and HCO3 − are well known to play an important role in glucose-stimulated insulin secretion (GSIS). In this study, we demonstrate that glucose-induced Cl− efflux from β-cells is mediated by the Ca2+-activated Cl− channel anoctamin 1 (Ano1). Ano1 expression in rat β-cells is demonstrated by reverse transcriptase–polymerase chain reaction, western blotting, and immunohistochemistry. Typical Ano1 currents are observed in whole-cell and inside-out patches in the presence of intracellular Ca++: at 1 μM, the Cl− current is outwardly rectifying, and at 2 μM, it becomes almost linear. The relative permeabilities of monovalent anions are NO3 − (1.83 ± 0.10) > Br− (1.42 ± 0.07) > Cl− (1.0). A linear single-channel current–voltage relationship shows a conductance of 8.37 pS. These currents are nearly abolished by blocking Ano1 antibodies or by the inhibitors 2-(5-ethyl-4-hydroxy-6-methylpyrimidin-2-ylthio)-N-(4-(4-methoxyphenyl)thiazol-2-yl)acetamide (T-AO1) and tannic acid (TA). These inhibitors induce a strong decrease of 16.7-mM glucose-stimulated action potential rate (at least 87 % on dispersed cells) and a partial membrane repolarization with T-AO1. They abolish or strongly inhibit the GSIS increment at 8.3 mM and at 16.7 mM glucose. Blocking Ano1 antibodies also abolish the 16.7-mM GSIS increment. Combined treatment with bumetanide and acetazolamide in low Cl− and HCO3 − media provokes a 65 % reduction in action potential (AP) amplitude and a 15-mV AP peak repolarization. Although the mechanism triggering Ano1 opening remains to be established, the present data demonstrate that Ano1 is required to sustain glucose-stimulated membrane potential oscillations and insulin secretion.
SCOPUS: ar.j
info:eu-repo/semantics/published
Databáze: OpenAIRE
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