Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain

Abstract

1. The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) receptors of neurones freshly dissociated from the olfactory bulb and olfactory tubercle has been studied using patch-clamp techniques. 2. Pentobarbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 microM. 3. Analysis of the NMDA-evoked noise produced power spectra that could be fitted by the sum of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobarbitone increased the corner frequency of the high frequency component but did not alter the apparent single channel conductance estimated from the noise. 4. Single channel recordings in either the cell-attached or outside-out patch configurations revealed that NMDA (20 or 50 microM) opened channels with a main conductance level around 55 pS and a principal subconductance around 44 pS. The uncorrected mean open time of the channels was 3.4 ms and mean burst length was 6.0 ms. Mean cluster length was about 12 ms. 5. Pentobarbitone produced a concentration-dependent reduction in both mean open time and burst length. Mean cluster length was much less affected. Pentobarbitone did not decrease unitary current amplitude or bias the open-state current amplitude distribution in favour of a particular substate. 6. From these data it appears that pentobarbitone depresses the inward current evoked by NMDA by reducing the probability of channel opening and this results from a shortening of the lifetime of the channel open state and by decreasing burst length.