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1. Neuropeptide Y (NPY) produced inhibitory effects on neurons of the thalamic reticular nucleus (RT; n = 18) and adjacent ventral basal complex (VB; n = 22), which included hyperpolarization (approximately 4 mV), a reduction in rebound and regular spikes and an increased membrane conductance. These effects were mediated predominantly via NPY1 receptor(More)
1. We have studied the kinetic properties of channel gating of recombinant alpha 1 beta 2 gamma 2L GABA(A) receptors transiently expressed in human embryonic kidney 293 cells, using the cell-attached, single-channel patch-clamp technique. The receptors were activated by GABA, beta-alanine or piperidine-4-sulfonic acid (P4S), and the effects of pentobarbital(More)
The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the(More)
1. The voltage dependence of binding and gating in wild-type and mutant recombinant mouse nicotinic acetylcholine receptors (AChRs) was examined at the single-channel level. 2. The closing rate constant of diliganded receptors decreased e-fold with approximately 66 mV hyperpolarization in both wild-type (adult and embryonic) and mutant receptors. The(More)
Synaptic inhibition in the thalamus plays critical roles in sensory processing and thalamocortical rhythm generation. To determine kinetic, pharmacological, and structural properties of thalamic gamma-aminobutyric acid type A (GABA(A)) receptors, we used patch-clamp techniques and single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in(More)
We have studied the effect of patch excision on the gating kinetics of muscle nicotinic acetylcholine receptors transiently expressed in HEK 293 cells. The experiments were performed on embryonic and adult wild-type, and several mutated, receptors using acetylcholine, carbamylcholine and tetramethylammonium as agonists. We show that patch excision of(More)
Neuroactive steroids are among the most efficacious modulators of the mammalian GABA-A receptor. Previous work has proposed that receptor potentiation is mediated by steroid interactions with a site defined by the residues alpha1Asn407/Tyr410 in the M4 transmembrane domain and residue alpha1Gln241 in the M1 domain. We examined the role of residues in the(More)
Neurosteroids are produced in the brain, and can have rapid actions on membrane channels of neurons. Pregnenolone sulfate (PS) is a sulfated neurosteroid which reduces the responses of the [gamma]-aminobutyric acid A (GABA(A)) receptor. We analysed the actions of PS on single-channel currents from recombinant GABA(A) receptors formed from [alpha]1, [beta]2(More)
Neuroactive steroids modulate the function of gamma-aminobutyric acid, type A (GABA(A)) receptors in the central nervous system by an unknown mechanism. In this study we have used a novel neuroactive steroid analogue, 3 alpha,5 beta-6-azi-3-hydroxypregnan-20-one (6-AziP), as a photoaffinity labeling reagent to identify neuroactive steroid binding sites in(More)
We have studied the ability of the androgen etiocholanolone and its enantiomer (ent-etiocholanolone) to modulate rat alpha1beta2gamma2L GABA(A) receptor function transiently expressed in human embryonic kidney cells. Studies on steroid enantiomer pairs can yield powerful new information on the pharmacology of steroid interactions with the GABA(A) receptor.(More)