NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron.
Early in development, GABA and glycine exert excitatory action that turns to inhibition due to modification of the chloride equilibrium potential (E(Cl)) controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and functional early in development (E11.5-E13.5) when GABA(A) receptor activation induces strong excitatory action. After E15.5, a switch occurs rendering GABA unable to provide excitation. At these subsequent stages, NKCC1 becomes both inactive and less abundant in motoneurons while KCC2 remains functional and hyperpolarizes E(Cl). In conclusion, in contrast to other systems, the cotransporters are concomitantly expressed early in the development of the mouse spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction, KCC2 is highly expressed throughout both early and late embryonic life.
Delpy
Alain
A
Centre de Neuroscience Intégratives et Cognitives, Université Bordeaux and CNRS, UMR 5228, Avenue des Facultés, 33405 Talence cedex, France.
Allain
Anne-Emilie
AE
Meyrand
Pierre
P
Branchereau
Pascal
P
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007539:Isonicotinic Acids / Q000494:pharmacology; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2; D013127:Spinal Nerves / Q000196:embryology* / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D000096922:K Cl- Cotransporters
D002034:Bumetanide; D002712:Chlorides; D005665:Furosemide; D018755:GABA Agonists; D007539:Isonicotinic Acids; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C578878:Slc12a2 protein, mouse; C015300:isoguvacine