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Cotransporter-mediated water transport underlying cerebrospinal fluid formation
Annette B Steffensen1, Eva K Oernbo1, Anca Stoica1
1Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Noerre Allé 14, 2200, Copenhagen, Denmark.
Nature Communications
|June 6, 2018
Summary
The Na+/K+/2Cl- cotransporter (NKCC1) in the choroid plexus drives half of cerebrospinal fluid production by coupling water and ion transport. This discovery redefines brain fluid dynamics and identifies a new drug target.
Area of Science:
- Neuroscience
- Physiology
- Molecular Biology
Background:
- Cerebrospinal fluid (CSF) production is vital for brain homeostasis, but its molecular mechanisms remain unclear.
- Existing models based on osmotic forces cannot fully explain the high rate of CSF production (500 ml/day).
Purpose of the Study:
- To identify the molecular machinery responsible for cerebrospinal fluid production.
- To elucidate the mechanisms of fluid transport across the choroid plexus.
Main Methods:
- Ex vivo live imaging of the choroid plexus.
- Isotope flux studies.
- In vivo determination of CSF production in mice.
Main Results:
- The Na+/K+/2Cl- cotransporter (NKCC1), located on the luminal membrane of the choroid plexus, was identified as a key component.
- NKCC1 accounts for approximately 50% of CSF production.
- NKCC1 facilitates CSF production through an unusual outward transport direction, directly coupling water transport to ion translocation.
Conclusions:
- Water cotransport is a critical, previously unrecognized mechanism in CSF production.
- This finding redefines the physiological model of CSF production.
- NKCC1 represents a potential pharmacological target for treating disorders of brain fluid dynamics.
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