Protein kinase M zeta enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors

Protein kinase M zeta (PKM zeta), a constitutively active, atypical PKC isoform, enhances synaptic strength during the maintenance of long-term potentiation (LTP). Here we examine the mechanism by which PKM zeta increases synaptic transmission. Postsynaptic perfusion of PKM zeta 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 PKM zeta enhancement showed that the kinase doubled the number of functional postsynaptic AMPAR channels. After sustained potentiation, application of a PKM zeta inhibitor reversed the increase in functional channel number to basal levels, suggesting that persistent increase of PKM zeta 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 PKM zeta functions specifically to establish and maintain long-term increases in active postsynaptic AMPAR number. (c) 2006 Wiley-Liss, Inc.