NMDA receptors regulate developmental gap junction uncoupling via CREB signaling.
Signaling through gap junctions (electrical synapses) is important in the development of the mammalian central nervous system. Abundant between neurons during postnatal development, gap junction coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. Here we report that developmental uncoupling of gap junctions in the rat hypothalamus in vivo and in vitro is associated with a decrease in connexin 36 (Cx36) protein expression. Both developmental gap junction uncoupling and Cx36 downregulation are prevented by the blockade of NMDA glutamate receptors, action potentials and the calcium-cyclic AMP response element binding protein (CREB), and are accelerated by CREB overexpression. Developmental gap junction uncoupling and Cx36 downregulation are not affected by blockade of non-NMDA glutamate receptors, and do not occur in hypothalamic neurons from NMDA receptor subunit 1 (NMDAR1) knockout mice. These results demonstrate that NMDA receptor activity contributes to the developmental uncoupling of gap junctions via CREB-dependent downregulation of Cx36.
Arumugam
Harsha
H
Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA.
Liu
Xinhuai
X
Colombo
Paul J
PJ
Corriveau
Roderick A
RA
Belousov
Andrei B
AB
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D017362:Cyclic AMP Response Element-Binding Protein; D016194:Receptors, N-Methyl-D-Aspartate; D000097004:Gap Junction delta-2 Protein