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Neurobiology

A homeostatic switch

Nature volume 397, pages 215–216 (1999)Cite this article

It started life in French as le contrôle du milieu interne, and then picked up a Greek name — homeostasis. The idea, that in whole animals or single cells physiological parameters are regulated close to a constant value, is an old one. But homeostatic fixed points can change. A shift in the concentration of chloride during development changes the signalling between neurons that release the neurotransmitter GABA (γ-aminobutyric acid) and their target cells from positive to negative. And, reporting on page 251 of this issue, Rivera et al.1 have pinned down a molecule that may be responsible for this switch.

A K+/Cl− co-transporter seems to be responsible for this switch. This molecule couples the outward movement of Cl− and potassium ions across the cell membrane, and has two known isoforms. One, KCC1, is a housekeeping protein expressed in most cells and involved in regulating cell volume. The other, KCC2, is specific to neurons2, and is thought to be crucial for regulating the concentration of intracellular Cl− (which is not distributed passively in these cells). Rivera and colleagues1 now show that expression of KCC2 in rat hippocampal cells begins about one week after birth — just when GABA responses switch from depolarizing to hyperpolarizing. To consolidate the link they show that, in adult cells, they can change the hyperpolarizing action of GABA back to a depolarizing effect by injecting antisense RNA sequences that bind KCC2 messenger RNA and stop it being produced. The authors conclude that expression of KCC2 is enough to change the cell's fixed point for Cl− from high to low.

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Figure 1: Chloride homeostasis and signalling by the inhibitory neurotransmitter GABA.

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  1. Laboratoire de Neurobiologie Cellulaire, INSERM U261, Institut Pasteur, 25 rue du Dr Roux, Paris, cedex 15, France

    Richard Miles

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Miles, R. A homeostatic switch. Nature 397, 215–216 (1999). https://doi.org/10.1038/16604

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