Bicuculline methiodide (BIC-MeI) (10-100 μM) altered the kinetics of N- methyl-D-aspartate (NMDA) responses in single-channel and whole-cell recordings. The principal effect of BIC-MeI (10-100 μM) on NMDA channels was a dose-dependent decrease in mean channel open time (τ(o)), accompanied by the introduction of a new closed time (τ(B)) of 14.0 ± 3.5 msec (mean ± standard deviation; n = 14) in closed time distributions, which was independent of BIC-MeI concentration. BIC-MeI (10-100 μM) increased the frequency of NMDA channel opening in a dose-dependent manner, offsetting the decrease in τ(o), such that the total time spent in the open state per minute was unchanged, and thus the total charge/min through NMDA channels was unchanged. Similarly, the amplitudes of NMDA whole-cell current responses were not noticeably affected by 10-80 μM BIC-MeI, even though power spectra density analysis of the whole-cell NMDA-stimulated noise revealed changes in the underlying channel kinetics in the presence of BIC-MeI. Taken together, the effects of 10-80 μM BIC-MeI on NMDA responses were consistent with the predictions of the sequential block model; however, the effects of BIC-MeI exhibited no obvious voltage dependence. In addition to the low-dose effects of BIC-MeI, 100 and 200 μM BIC-MeI inhibited whole-cell NMDA responses. The inhibition by 100 μM BIC-MeI was not large, but it was augmented from 15% to 30% by increasing the NMDA concentration from 10 μM NMDA to 20 μM NMDA, indicating that channel activation was necessary for BIC-MeI-mediated inhibition. Preliminary single-channel experiments performed under conditions conducive to trapping of an open channel blocker at its binding site indicated that the effect of BIC-MeI on τ(o) persisted after the removal of the blocker, consistent with use dependence of the dissociation of BIC-MeI from the NMDA receptor-channel complex.
|Original language||English (US)|
|Number of pages||8|
|State||Published - 1992|
ASJC Scopus subject areas
- Molecular Medicine