Changes of spontaneous miniature excitatory postsynaptic currents in rat hippocampal pyramidal cells induced by aniracetam

Spontaneous miniature excitatory postsynaptic currents (mEPSCs) in rat hippocampal pyramidal neurones in slices (CA1 region) were recorded at 35–37°C using the whole-cell patch-clamp technique before and after addition of aniracetam (1 mM) to determine how a partial blockade of desensitization alters the relationship between the amplitude (A) and kinetics of mEPSCs, and to evaluate the factors that determine their variability. The rise time (τr) and the time constant of decay of mEPSCs (τd) are essentially amplitude independent in control conditions, but become clearly amplitude dependent in the presence of aniracetam. The slopes of the best fitting lines to τd:A and τr:A data pairs were (± SD; ms/pA; n = 5): (1) (control) 0.07 ± 0.02 and 0.008 ± 0.003; (2) (aniracetam) 0.40 ± 0.19 and 0.22 ± 0.22. The amplitude-dependent prolongation of τd is explained by the concentration dependence of two related processes, the buffering of glutamate molecules by AMPA receptor channels, and the occupancy of the double-bound activatable states. A slower deactivation makes an amplitude-independent contribution. Desensitization reduces the amplitude dependence of τd by minimizing repeated openings of α-amino-3-hydroxy-methyl-isoxazole (AMPA) receptor channels. A greater amplitude dependence of τr probably involves both pre- and postsynaptic factors. The variability of A and τd values did not change significantly, but the factors underlying the variability of τd values were much affected. The greater amplitude dependence and the greater scatter about the best fitting lines to τd:A data pairs are approximately balanced by the greater mean values. The greater scatter of τd about the best fitting lines probably occurs because the saturation of AMPA receptors is not the same at different synapses with different numbers of AMPA receptors.