Molecular Basis of Neural Signalling

The nicotinic acetylcholine receptor （AChR） is an archetypal neurotransmitter-gated ionic channel. Structure-function relationships of the nicotinic AChR have been studied by analysing the functional properties of receptors of different subunit compositions produced by expression of the corresponding cDNAs and those of mutant receptors produced by expression of the cDNAs altered by site-directed mutagenesis. For example, the single-channel properties of bovine nicotinic AChRs of different subunit compositions, in conjunction with the developmental changes observed in the muscular contents of the subunit mRNAs, suggest that replacement of the γ-subunit by the ε-subunit is responsible for the functional alteration of the nicotinic AChR during muscle development. Furthermore, functional analysis of nicotinic AChR mutants generated by site-directed mutagenesis indicates that three clusters of negatively charged and glutamine residues neighbouring the hydrophobic segment M2 of the α-, β-, γ- and δ-subunits, probably forming the three anionic rings, are major determinants of the rate of ion transport through the channel. The muscarinic AChR mediates a variety of cellular responses through the action of guanine nucleotide-binding regulatory proteins. The existence and the primary structures of multiple muscarinic AChR species have been revealed by cloning and sequence analysis of the cDNAs. The antagonist-binding properties of the individual muscarinic AChR species expressed from cDNAs (or genomic DNAs), together with the differential tissue location of the mRNAs encoding them, indicate that the muscarinic AChR heterogeneity in tissues with respect to antagonist binding can be accounted for by the presence of individual molecularly distinct muscarinic AChR species or various combinations of them. The agonist-induced responses in NG108-15 neuroblastoma-glioma hybrid cells and Xenopus oocytes expressing the individual muscarinic AChR subtypes are selectively coupled with different effector systems, albeit not exclusively