TY - JOUR
T1 - Coupled activity-dependent trafficking of synaptic SK2 channels and AMPA receptors
AU - Lin, Mike T.
AU - Luján, Rafael
AU - Watanabe, Masahiko
AU - Frerking, Matthew
AU - Maylie, James
AU - Adelman, John P.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Small conductance Ca2+-activated K+ type 2 (SK2) channels are expressed in the postsynaptic density of CA1 neurons where they are activated by synaptically evoked Ca2+ influx to limit the size of EPSPs and spine Ca2+ transients. At Schaffer collateral synapses, the induction of long-term potentiation (LTP) increases the α-amino-3- hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)-mediated contribution to synaptic transmission and decreases the synaptic SK2 channel contribution through protein kinase A-dependent channel endocytosis. Using a combination of electrophysiology and immunoelectron microscopy in mice, the relationship between the dynamics of spine SK2 channels and AMPARs was investigated. Unlike AMPARs, synaptic SK2 channels under basal conditions do not rapidly recycle. Furthermore, SK2 channels occupy a distinct population of endosomes separate from AMPARs. However, blocking vesicular exocytosis or the delivery of synaptic GluA1-containing AMPARs during the induction of LTP blocks SK2 channel endocytosis. By ∼2 h after the induction of LTP, synaptic SK2 channel expression and function are restored. Thus, LTP-dependent endocytosis of SK2 is coupled to LTP-dependent AMPA exocytosis, and the ∼2 h window after the induction of LTP during which synaptic SK2 activity is absent may be important for consolidating the later phases of LTP.
AB - Small conductance Ca2+-activated K+ type 2 (SK2) channels are expressed in the postsynaptic density of CA1 neurons where they are activated by synaptically evoked Ca2+ influx to limit the size of EPSPs and spine Ca2+ transients. At Schaffer collateral synapses, the induction of long-term potentiation (LTP) increases the α-amino-3- hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)-mediated contribution to synaptic transmission and decreases the synaptic SK2 channel contribution through protein kinase A-dependent channel endocytosis. Using a combination of electrophysiology and immunoelectron microscopy in mice, the relationship between the dynamics of spine SK2 channels and AMPARs was investigated. Unlike AMPARs, synaptic SK2 channels under basal conditions do not rapidly recycle. Furthermore, SK2 channels occupy a distinct population of endosomes separate from AMPARs. However, blocking vesicular exocytosis or the delivery of synaptic GluA1-containing AMPARs during the induction of LTP blocks SK2 channel endocytosis. By ∼2 h after the induction of LTP, synaptic SK2 channel expression and function are restored. Thus, LTP-dependent endocytosis of SK2 is coupled to LTP-dependent AMPA exocytosis, and the ∼2 h window after the induction of LTP during which synaptic SK2 activity is absent may be important for consolidating the later phases of LTP.
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U2 - 10.1523/JNEUROSCI.1411-10.2010
DO - 10.1523/JNEUROSCI.1411-10.2010
M3 - Article
C2 - 20810893
AN - SCOPUS:77956257846
SN - 0270-6474
VL - 30
SP - 11726
EP - 11734
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 35
ER -