KCC2 expression in immature rat cortical neurons is sufficient to switch the polarity of GABA responses.
During brain development, GABA and glycine switch from being depolarizing to being hyperpolarizing neurotransmitters. This conversion results from a gradual decrease in the chloride electrochemical equilibrium potential (ECl) of developing neurons, which correlates to an increase in the expression or activity of the potassium chloride cotransporter, KCC2. However, evidence as to whether KCC2 expression is sufficient, in and of itself, to induce this switch is lacking. In order to address this question, we used a gain-of-function approach by over-expressing human KCC2 (hKCC2) in immature cortical neurons, before endogenous up-regulation of KCC2. We found that premature expression of hKCC2 produced a substantial negative shift in the GABA reversal potential and decreased or abolished GABA-elicited calcium responses in cultured neurons. We conclude that KCC2 expression is not only necessary but is also sufficient for ending the depolarizing period of GABA in developing cortical neurons.
Lee
Hanmi
H
Department Neurobiology, University of Pittsburgh School of Medicine, W1447 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
Chen
Carol Xiu-Qing
CX
Liu
Yong-Jian
YJ
Aizenman
Elias
E
Kandler
Karl
K
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental; D005998:Glycine / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000502:physiology*; D000096922:K Cl- Cotransporters
D002118:Calcium; D005998:Glycine; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters