Relationships between the kinetic properties of AMPA receptors and the decay phase of fast excitatory transmission were investigated using modulatory drugs. The benzothiadiazide compound cyclothiazide blocked receptor desensitization in patches excised from hippocampus but had only a weak influence on receptor deactivation, i.e., on the decay of responses produced by a 1-ms pulse of glutamate. The ampakine drug CX516 (BDP-12) produced an opposite pattern of effects: a fourfold slowing of deactivation with little change in desensitization. A structurally related drug (CX554 or BDP-20) had prominent effects on both desensitization and deactivation. The halfwidth of field EPSPs measured in the CA1 region of hippocampal slices increased 50-100% in the presence of CX516 or CX554 but by less than 15% at concentrations of cyclothiazide that fully blocked desensitization in patch experiments. These results indicate that receptor deactivation plays a substantially greater role than receptor desensitization in determining the duration of synaptic responses.
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