PENTOBARBITAL MODULATION OF NMDA RECEPTORS IN NEURONS ISOLATED FROM THE RAT OLFACTORY BRAIN

Citation
P. Charlesworth et al., PENTOBARBITAL MODULATION OF NMDA RECEPTORS IN NEURONS ISOLATED FROM THE RAT OLFACTORY BRAIN, British Journal of Pharmacology, 116(7), 1995, pp. 3005-3013
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
116
Issue
7
Year of publication
1995
Pages
3005 - 3013
Database
ISI
SICI code
0007-1188(1995)116:7<3005:PMONRI>2.0.ZU;2-0
Abstract
1 The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) rece ptors of neurones freshly dissociated from the olfactory bulb and olfa ctory tubercle has been studied using patch-clamp techniques. 2 Pentob arbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 mu M. 3 Analysis of the N MDA-evoked noise produced power spectra that could be fitted by the su m of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobar bitone increased the corner frequency of the high frequency component but did not alter the apparent single channel conductance estimated fr om the noise.4 Single channel recordings in either the cell-attached o r outside-out patch configurations revealed that NMDA (20 or 50 mu M) opened channels with a main conductance level around 55 pS and a princ ipal subconductance around 44 pS. The uncorrected mean open time of th e channels was 3.4 ms and mean burst length was 6.0 ms. Mean cluster l ength was about 12 ms. 5 Pentobarbitone produced a concentration-depen dent reduction in both mean open time and burst length. Mean cluster l ength was much less affected. Pentobarbitone did not decrease unitary current amplitude or bias the open-state current amplitude distributio n in favour of a particular substate. 6 From these data it appears tha t pentobarbitone depresses the inward current evoked by NMDA by reduci ng the probability of channel opening and this results from a shorteni ng of the lifetime of the channel open state and by decreasing burst l ength.