Permeability Control and Desensitization by Nicotinic Acetylcholine Receptors

Abstract

The nicotinic acetylcholine (ACh) receptor is the best understood example of a neurotransmitter receptor that uses the energy of ligand binding to regulate directly the opening and closing of an ion channel (for recent reviews, see 1–3). Ion currents associated with the activation of individual receptors can be monitored in isolated muscle cells, and these studies provide clear evidence that individual channels exist in either “open” or “closed” states with transitions between states occurring rapidly. The ACh receptor has been purified to homogeneity, initially from detergent extracts of Torpedo electric tissue, and more recently from vertebrate skeletal muscle. The isolated receptor is a complex macromolecule (Mr250,000) that contains five subunits with stoichiometry α₂βγδ (4). Purifed ACh receptors have been reincorporated into artificial lipid bilayers (2,5,6), and it is clear that the protein purified on the basis of ligand binding properties also contains the structure of the ion channel. The complete amino acid sequence of each subunit has now been elucidated by sequencing cloned, complementary DNAs (cDNAs), and cloned cDNAs encoding all receptor subunits have been expressed together to produce functional receptors in Xenopus oocytes (7,8).