TY - JOUR
T1 - Calcium-induced actin depolymerization reduces NMDA channel activity
AU - Rosenmund, C.
AU - Westbrook, G. L.
N1 - Funding Information:
This work was supported by USPHS grant MH46613 and the Tartar Research Foundation. We thank Jeff Volk for the preparation of the cell cultures and Dr. Ven Narayanan (Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program, Division of Cancer Treatment, NCI, NIH) for the generous gift of taxol.
PY - 1993/5
Y1 - 1993/5
N2 - Actin filaments are highly concentrated in postsynaptic densities at central excitatory synapses, but their influence on postsynaptic glutamate receptors is unknown. We tested whether actin depolymerization influences NMDA channel activity in whole-cell recording on cultured hippocampal neurons. The ATP- and calcium-dependent rundown of NMDA channels was prevented when actin depolymerization was blocked by phalloidin. Rundown of AMPA/kainate receptors was unaffected by phalloidin. Cytochalasins, which enhance actin-ATP hydrolysis, induced NMDA channel rundown, whereas taxol or colchicine, which stabilize or disrupt microtubule assembly, had no effect. Protease inhibitors also had no effect. Our results suggest that calcium and ATP can influence NMDA channel activity by altering the state of actin polymerization and are consistent with a proposed model in which actin filaments compartmentalize a channel regulatory protein.
AB - Actin filaments are highly concentrated in postsynaptic densities at central excitatory synapses, but their influence on postsynaptic glutamate receptors is unknown. We tested whether actin depolymerization influences NMDA channel activity in whole-cell recording on cultured hippocampal neurons. The ATP- and calcium-dependent rundown of NMDA channels was prevented when actin depolymerization was blocked by phalloidin. Rundown of AMPA/kainate receptors was unaffected by phalloidin. Cytochalasins, which enhance actin-ATP hydrolysis, induced NMDA channel rundown, whereas taxol or colchicine, which stabilize or disrupt microtubule assembly, had no effect. Protease inhibitors also had no effect. Our results suggest that calcium and ATP can influence NMDA channel activity by altering the state of actin polymerization and are consistent with a proposed model in which actin filaments compartmentalize a channel regulatory protein.
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U2 - 10.1016/0896-6273(93)90197-Y
DO - 10.1016/0896-6273(93)90197-Y
M3 - Article
C2 - 7684233
AN - SCOPUS:0027258451
SN - 0896-6273
VL - 10
SP - 805
EP - 814
JO - Neuron
JF - Neuron
IS - 5
ER -