Journal
CELLS
Volume 9, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/cells9122607
Keywords
Slc12a2; ion regulation; chloride; GABA; epilepsy; NKCC1; KCC2
Categories
Funding
- Academy of Finland [319237, 294375, 321698]
- European Research Council [ERC-2013-AdG 341116]
- Sigrid Juselius Foundation
- German Research Foundation [RTG 1715, SPP 1665]
- Federal Ministry of Education and Research (NEURON ACRoBAT)
- Academy of Finland (AKA) [321698, 319237, 294375, 319237, 294375, 321698] Funding Source: Academy of Finland (AKA)
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Ionotropic GABA transmission is mediated by anion (mainly Cl-)-permeable GABA(A) receptors (GABA(A)Rs). In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl- by the Na-K-2Cl cotransporter NKCC1. While functional evidence firmly shows NKCC1-mediated ion transport in immature and diseased neurons, molecular detection of NKCC1 in the brain has turned out to be extremely difficult. In this review, we describe the highly inconsistent data that are available on the cell type-specific expression patterns of the NKCC1 mRNA and protein in the CNS. We discuss the major technical caveats, including a lack of knock-out-controlled immunohistochemistry in the forebrain, possible effects of alternative splicing on the binding of antibodies and RNA probes, and the wide expression of NKCC1 in different cell types, which make whole-tissue analyses of NKCC1 useless for studying its neuronal expression. We also review novel single-cell RNAseq data showing that most of the NKCC1 in the adult CNS may, in fact, be expressed in non-neuronal cells, especially in glia. As future directions, we suggest single-cell NKCC1 mRNA and protein analyses and the use of genetically tagged endogenous proteins or systematically designed novel antibodies, together with proper knock-out controls, for the visualization of endogenous NKCC1 in distinct brain cell types and their subcellular compartments.
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