CALCIUM-INDUCED ACTIN DEPOLYMERIZATION REDUCES NMDA CHANNEL ACTIVITY

Actin filaments are highly concentrated in postsynaptic densities at c entral excitatory synapses, but their influence on postsynaptic glutam ate receptors is unknown. We tested whether actin depolymerization inf luences NMDA channel activity in whole-cell recording on cultured hipp ocampal neurons. The ATP- and calcium-dependent rundown of NMDA channe ls was prevented when actin depolymerization was blocked by phalloidin . Rundown of AMPA/kainate receptors was unaffected by phalloidin. Cyto chalasins, which enhance actin-ATP hydrolysis, induced NMDA channel ru ndown, whereas taxol or colchicine, which stabilize or disrupt microtu bule assembly, had no effect. Protease inhibitors also had no effect. Our results suggest that calcium and ATP can influence NMDA channel ac tivity by altering the state of actin polymerization and are consisten t with a proposed model in which actin filaments compartmentalize a ch annel regulatory protein.