Coupled activity-dependent trafficking of synaptic SK2 channels and AMPA receptors.
Small conductance Ca(2+)-activated K(+) type 2 (SK2) channels are expressed in the postsynaptic density of CA1 neurons where they are activated by synaptically evoked Ca(2+) influx to limit the size of EPSPs and spine Ca(2+) transients. At Schaffer collateral synapses, the induction of long-term potentiation (LTP) increases the alpha-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 approximately 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 approximately 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.
Lin
Mike T
MT
Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Luján
Rafael
R
Watanabe
Masahiko
M
Frerking
Matthew
M
Maylie
James
J
Adelman
John P
JP
D000818:Animals; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D055366:Synaptic Potentials / Q000502:physiology
C496898:Kcnn2 protein, mouse; D018091:Receptors, AMPA; D051640:Small-Conductance Calcium-Activated Potassium Channels
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