| Co-Investigator(Kenkyū-buntansha) |
KUBO TAI Kyoto University,Faculty of Medicine, 医学部, 助手 (10178030)
SHIBAHARA SHIGEKI Kyoto University,Faculty of Medicine, 医学部, 助手 (00154253)
NODA MASAHARU Kyoto University,Faculty of Medicine, 医学部, 助教授 (60172798)
MISHINA MASAYOSHI Kyoto Umiversity,Faculty of Medicine, 医学部, 助教授 (80144351)
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| Research Abstract |
Neurotransmitter receptors and ionic channels are membrane proteins essential for neural signalling. The primary structures of the nicotinic acetylcholine receptor (nAChR), the sodium channel, the receptor for calcium channel blockers (putative calcium channel) and the muscarinic acetylcholine receptor (mAChR) have been deduced by cloning and sequence analysis of the cDNAs. The structural information thus obtained has ledto the identification of three families of evolutionarily related receptor and channel proteins, that is, neurotransmitter-gated ionic channels, voltage-gated ionic channels and G-protein-coupled receptors. In addition, a novel muscle nAChR subunit (named the -subunit) and three distinct brain sodium channels have been discovered by cloning and sequencing the cDNAs. Expression of the cloned cDNAs yields functional nAChR, sodium channel and mAChR in Xenopus oocytes. Functional analysis of nAChRs of different subunit compositions, produced by expression of the corresponding cDNAs, reveals roles of subunits in agonist binding, the gating of the channel and the functional alteration of the nAChR during muscle development. Furthermore, analysis of nAChR mutants produced by expression of the cDNAs altered by site-directed mutagenesis allows the location of functional regions involved in agonist binding and in determining the rate of ion transport through the channel. The functional properties of the sodium channel expressed have been studied. It has been shown that pharmacologically distinguishable subtypes of the mAChR represent distinct gene products.
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