Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin.
Modification of synaptic strength in the mammalian central nervous system (CNS) occurs at both pre- and postsynaptic sites. However, because postsynaptic receptors are likely to be saturated by released transmitter, an increase in the number of active postsynaptic receptors may be a more efficient way of strengthening synaptic efficacy. But there has been no evidence for a rapid recruitment of neurotransmitter receptors to the postsynaptic membrane in the CNS. Here we report that insulin causes the type A gamma-aminobutyric acid (GABA[A]) receptor, the principal receptor that mediates synaptic inhibition in the CNS, to translocate rapidly from the intracellular compartment to the plasma membrane in transfected HEK 293 cells, and that this relocation requires the beta2 subunit of the GABA(A) receptor. In CNS neurons, insulin increases the expression of GABA(A) receptors on the postsynaptic and dendritic membranes. We found that insulin increases the number of functional postsynaptic GABA(A) receptors, thereby increasing the amplitude of the GABA(A)-receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) without altering their time course. These results provide evidence for a rapid recruitment of functional receptors to the postsynaptic plasma membrane, suggesting a fundamental mechanism for the generation of synaptic plasticity.
Wan
Q
Q
Division of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.
Xiong
Z G
ZG
Man
H Y
HY
Ackerley
C A
CA
Braunton
J
J
Lu
W Y
WY
Becker
L E
LE
MacDonald
J F
JF
Wang
Y T
YT
D000200:Action Potentials; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011940:Receptor Aggregation; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection
D007328:Insulin; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter