The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion
Abstract Intracellular chloride concentration ([Cl−]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl− loaders such as the Na+K+2Cl− co-transporter 1 (Slc12a2) over Cl−extruders of unidentified nature. Using molecular cloning, RT-PCR,...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d1c00f15f43e41669bcde19b13071f67 |
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| Sumario: | Abstract Intracellular chloride concentration ([Cl−]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl− loaders such as the Na+K+2Cl− co-transporter 1 (Slc12a2) over Cl−extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the “neuron-specific” K+Cl− co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response. Three KCC2 splice variants were identified: the formerly described KCC2a and KCC2b along with a novel one lacking exon 25 (KCC2a-S25). This new variant is undetectable in brain or spinal cord, the only and most abundant known sources of KCC2. Inhibition of KCC2 activity in clonal MIN6 β-cells increases basal and glucose-stimulated insulin secretion and Ca2+ uptake in the presence of glibenclamide, an inhibitor of the ATP-dependent potassium (KATP)-channels, thus suggesting a possible mechanism underlying KCC2-dependent insulin release. We propose that the long-time considered “neuron-specific” KCC2 co-transporter is expressed in pancreatic islet β-cells where it modulates Ca2+-dependent insulin secretion. |
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