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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)
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)
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)
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)
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)
GABAA receptors are a pivotal inhibitory influence in the nervous system, and modulators of the GABAA receptor are important anesthetics, sedatives, anticonvulsants, and anxiolytics. Current views of receptor modulation suggest that many exogenous drugs access and bind to an extracellular receptor domain. Using novel synthetic steroid analogs, we examined(More)
We describe a maximum likelihood method for direct estimation of rate constants from macroscopic ion channel data for kinetic models of arbitrary size and topology. The number of channels in the preparation, and the mean and standard deviation of the unitary current can be estimated, and a priori constraints can be imposed on rate constants. The method(More)
Genome-wide association studies have identified common variation in the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking(More)
The properties of adult mouse recombinant nicotinic acetylcholine receptors activated by acetylcholine (ACh+) or tetramethylammonium (TMA+) were examined at the single-channel level. The midpoint of the dose-response curve depended on the type of monovalent cation present in the extracellular solution. The shifts in the midpoint were apparent with both(More)