Acetylcholine ligand-gated channels

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

Many receptors for neurotransmitters function as ligand-gated channels for Na and/or Ca " ions (see p. 354). The ones that have been studied in the greatest detail are the nicotinic receptors for acetylcholine (see p. 352). These consist of five separate but structurally closely related subunits. Each forms four transmembrane helices, the second of which is involved in the central pore in each case. The type of monomer and its arrangement in the complex is not identical in all receptors of this type. In the neuromuscular junction (see p. 334), the arrangement aPya8 is found (1). 

Ligand-gated channels, which may either open or close in response to ligand binding. Important examples are the nicotinic acetylcholine receptor, which allows Na into the cell in response to acetylcholine, and the sulfonylurea receptor-associated Kj. channel, which ceases to permit efflux of in response to ATR... 

Several transmitters - acetylcholine, glutamate, serotonin, GABA, and adenosine and its various phosphates - have receptors both among the ligand-gated channels and the G protein-coupled receptors. Thus, these transmitters evidently serve multiple purposes in the nervous system. 

How do ion chaimels, vital to a wide array of biological functions, operate at a molecular level We will examine three chaimels important in the propagation of nerve impulses the ligand-gated channel the acetylcholine receptor channel, which communicates the nerve impulse between certain neurons and the voltage-gated Na+ and K+ channels, which conduct the nerve impulse down the axon of a neuron. 

Ligand-gated channels are activated by binding of an agonist to the exctracellular domain of the channel. Examples are provided by the acetylcholine receptor and the N-methyl-D-asparate receptor. 

The acetylcholine receptor is the best-understood ligand-gated channel. The activity of a single such channel is graphically displayed in patch-clamp... 

Explain the function of neurotransmitters and ligand-gated channels in the transmission of nerve impulses across synapses. Outline the effects of acetylcholine on the post-synaptic membrane. 

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... 

Changeux, JP (1990) The nicotinic acetylcholine receptor an allosteric protein protot5q)e of ligand-gated ion channels. Trends Pharmacol. Sci. 11 485M92. 

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