The nicotinic acetylcholine receptor and its ion channel

Abstract

Extracellular signals are transduced to the cytoplasm by receptor proteins. In the case of most hormones and all neurotransmitters, these receptors are located in the plasma membrane and convey the signal from outside the cell to the inside, not directly but via second messengers. Depending on whether the second messenger is an ion or a low-molecularmass compound like CAMP, the receptor therefore is coupled to an ion channel (type I) or an enzyme catalysing the synthesis of the second messenger (type 11). A prototype of the channelcoupled type I receptors is the nicotinic acetylcholine receptor (nAChR), found at the neuromuscular endplate, in the central nervous system and in a variety of peripheral ganglia and tissues. A prototype of the enzyme-coupled type I1 receptors is the p-adrenergic receptor.The wealth of biochemical information accumulated over the past fifteen years makes the nAChR the best-known receptor; extrapolation of the present rate of progress makes it likely to be the first receptor to be completely elucidated in the near future.

G Protein-independent Activation of an Inward Na+Current by Muscarinic Receptors in Mouse Pancreatic β-Cells

“…This is fully compatible with the persistence of the AChinduced inward current in a K ϩ -free medium, another situation where the Na ϩ pump is blocked. Nicotinic receptors, which are nonselective cationic channels (28,29), classically mediate cholinergic effects on Na ϩ currents. Such channels are clearly not responsible for the AChinduced inward current in ␤-cells because the muscarinic antagonist atropine completely prevented the current and the rise in [Na ϩ ] c (15), whereas the ACh-activated current was not mimicked by nicotine and was insensitive to nicotinic antagonists.…”

The noncompetitive blocker [3H]chlorpromazine labels segment M2 but not segment M 1 of the nicotinic acetylcholine receptor α‐subunit

“…The nicotinic acetylcholine receptor (AChR) from vertebrate muscle and fish electric organ is a heterologous pentamer (ot2BTt~) which carries the acetylcholine-binding sites and contains the cationselective channel forming elements [3,4]. The noncompetitive blockers (NCBs) are compounds that block the permeability response by interfering directly and/or indirectly with the functioning of the ion channel [5].…”

Interaction of modified neurotoxins fromNaja nigricollis with the nicotinic acetylcholine receptor fromTorpedo marmorata A Raman spectroscopy study

“…This allosteric membrane protein of 300 kDa possesses a pentameric 'heterologous' organisation cz~76 where each czsubunit carried a binding site of neurotoxins. Its initial identification from fish electric organ [I] and the subsequent characterisation of its functional architecture [2][3][4] has received considerable help from the utilisation of snake venom cz-toxins [5][6][7] which behave as competitive antagonists of the physiological response and bind in a highly selective and slowly reversible manner to the acetylcholine binding site. The AcCho receptor-~-toxin complex displays a very low dissociation constant (Kd=2xl0 -~ M) suggesting that multiple side-chain interactions take place in toxin-receptor binding [8].…”