Ion channel, ligand-gated

Two related models describing the rapid inactivation process of the Na channel or chaimel are generally accepted and are backed up experimentally. Both models are based on conformational changes in which flexible structural elements of the central subimit align themselves in the entrance to the pore from the intracellular side and temporarily block it. 

The function of the ion channels is also regulated by phosphorylation of intracellular structural elements. The biochemical basis of this regulation is poorly understood. 

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Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

Fig. 1. Model of a ligand gated ion channel (LGIC) where (a) is the structure of a generic LGIC subunit showing the two cysteine (Cys) residues common to all LGIC subunits, and (b) shows the arrangement of five such subunits as a pentamer having psuedo-cyclic symmetry delineating a gated, fluid-filled...

Krasowski MD, Harrison NL (1999) General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 55 1278-1303... 

A number of agonists can act through several receptor classes, e.g., ion channels and G-protein-coupled receptors. To set receptor subtypes permanently linked to ion channels ( ligand-gated ion channels) apart... 

For differentiation of G-protein-coupled receptor sub-types from subtypes permanently linked to ion channels (ligand-gated ion channels) the terms metabotropic versus ionotropic receptors, respectively, are used. Prime examples of metabotropic receptors are given by the lnGlu receptor family of G-protein-coupled glutamate receptors. 

Neurotransmitter transport can be electrogenic if it results in the net translocation of electrical charge (e.g. if more cations than anions are transferred into the cell interior). Moreover, some transporters may direction-ally conduct ions in a manner akin to ligand-gated ion channels this ion flux is not coupled to substrate transport and requires a separate permeation pathway associated with the transporter molecule. In the case of the monoamine transporters (DAT, NET, SERT) the sodium current triggered by amphetamine, a monoamine and psychostimulant (see Fig. 4) is considered responsible for a high internal sodium concentration... 

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

HT3 receptors belong to the ligand-gated ion channel receptor superfamily, similar to the nicotinic acetylcholine or GABAa receptors and share elec-trophysiological and structural patterns. The receptors... 

Synaptic Transmission. Figure 1 Synaptic transmission. The presynaptic terminal contains voltage-dependent Na Superscript and Ca2+ channels, vesicles with a vesicular neurotransmitter transporter VNT, a plasmalemmal neurotransmitter transporter PNT, and a presynaptic G protein-coupled receptor GPCR with its G protein and its effector E the inset also shows the vesicular H+ pump. The postsynaptic cell contains two ligand-gated ion channels LGIC, one for Na+ and K+ and one for Cl-, a postsynaptic GPRC, and a PNT. In this synapse, released transmitter is inactivated by uptake into cells. 

Of the several classes of receptors for endogenous chemical signals [3], two are used as postsynaptic receptors in synaptic transmission ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs Fig. 1). Due to the large number of transmitters and the existence of several receptor types for almost all, postsynaptic receptor activation is the most diversified step of synaptic transmission. Table 1 shows selected neurotransmitter receptors. 

Inhalants appear to have significant effects on a superfamily of ligand-gated ion channels, including the GABAj receptor, the glycine receptor, the nico-... 

Ortells MO, Lunt GG Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci 18 121—127, 1995 Overall JE, Gorham DR The Brief Psychiatric Rating Scale. Psychol Rep 10 799—812,1962 Payne JP The criminal use of chloroform. Anaesthesia 53 685—690, 1998... 

Yamakura T, Harris RA Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels comparison with isoflurane and ethanol. Anesthesiology 93 1093-1101,2000... 

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