Protein kinase Mzeta enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors.
Protein kinase Mzeta (PKMzeta), a constitutively active, atypical PKC isoform, enhances synaptic strength during the maintenance of long-term potentiation (LTP). Here we examine the mechanism by which PKMzeta increases synaptic transmission. Postsynaptic perfusion of PKMzeta during whole-cell recordings of CA1 pyramidal cells strongly potentiated the amplitude of AMPA receptor (AMPAR)-mediated miniature EPSCs (mEPSCs). Nonstationary fluctuation analysis of events recorded before and after PKMzeta enhancement showed that the kinase doubled the number of functional postsynaptic AMPAR channels. After sustained potentiation, application of a PKMzeta inhibitor reversed the increase in functional channel number to basal levels, suggesting that persistent increase of PKMzeta is required to maintain the postsynaptic localization of a mobile subpopulation of receptors. The kinase did not affect other sites of LTP expression, including presynaptic transmitter release, silent synapse conversion, or AMPAR unit conductance. Thus PKMzeta functions specifically to establish and maintain long-term increases in active postsynaptic AMPAR number.
Ling
Douglas S F
DS
Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203, USA. douglas.ling@downstate.edu
Benardo
Larry S
LS
Sacktor
Todd C
TC
D000818:Animals; D003712:Dendrites / Q000187:drug effects; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D018091:Receptors, AMPA; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat