Chemistry of Synapses and Synaptic Transmission in the Nervous System of Insects
01 Jan 1986-pp 91-115
TL;DR: Due to the strategical role, synapses and synaptic transmission are central for understanding how the nervous system works and great efforts are presently made to explore aspects of synaptic transmission in molecular detail.
Abstract: Neurons are the elementary signalling units of the nervous system which differ from other cells in their highly developed ability to generate signals and to communicate with another and with other target cells rapidly, precisely and over long distances. The communication between neurons occurs at specialized structures, the synapses, by means of precisely regulated release of primary messenger molecules, which effectively react on specialized regions of the postsynaptic cell, triggering changes in the permeability and the potential of the membranes either directly or via cellular second messenger molecules. Thus synaptic transmission is considered a fundamental process in neuronal function and it is reasonable to speculate that higher functions in the central nervous system must involve specific structural and molecular elements of synapses. Due to the strategical role, synapses and synaptic transmission are central for understanding how the nervous system works and great efforts are presently made to explore aspects of synaptic transmission in molecular detail.
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TL;DR: It is concluded that embryonic cockroach neurones growing in vitro possess two populations of acetylcholine-activated ion channels, and the possibility that one of these represents an embryonic receptor and the other an adult receptor is discussed.
Abstract: Summary Application of acetylcholine and carbamylcholine to cultured cockroach neurones held under whole-cell voltage-clamp conditions evoked an inward current that was accompanied by an increase in current noise. Fluctuation analysis of the noise revealed the existence of two Lorentzian components in acetylcholine, of corner frequencies 10 ± 0-6 Hz and 116 ± 9 Hz, and one Lorentzian component in carbamylcholine, of corner frequency 35 ± 13 Hz. Single-channel analysis of the unitary currents evoked by acetylcholine or carbamylcholine in neurones held in the cell-attached mode of the patch-clamp technique revealed the presence of two categories of channel events. The large events had mean currents of 4-77 pA with acetylcholine and 5-09 pA with carbamylcholine, and the small events 1-92 pA (acetylcholine) and l-72pA (carbamylcholine) for a hyperpolarization of 60 mV. The reversal potentials for these currents relative to the resting potential were estimated to be — 70 mV for acetylcholine and — 68 mV for carbamylcholine, and the conductance values calculated from the I/V curves were 37 pS (large) and 19 pS (small) for acetylcholine and 52 pS (large) and 15 pS (small) for carbamylcholine. It is concluded that embryonic cockroach neurones growing in vitro possess two populations of acetylcholine-activated ion channels, and the possibility that one of these represents an embryonic receptor and the other an adult receptor is discussed.
26 citations
TL;DR: The deduced amino acid sequences of these subunits share several features (notably four hydrophobic predicted membrane-spanning domains) and are related to several closely related oL(1_3) and 13(1-3) subunit variants from mammalian brain.
Abstract: y-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the vertebrate central nervous system, acts upon two different receptor types--GABAA and GABAB (1). The principal neuronal response to GABA, a rapid hyperpolarizing increase in membrane chloride permeability, is mediated by receptors of the GABAA subtype. This receptor is a transmembrane protein (2, 3) containing an integral chloride channel which is directly gated by the binding of GABA (4). Initial characterization of the purified receptor showed it to consist of two glycosylated polypeptide subunits, designated c~ and 13 (reviewed in Ref. 5). Subsequent molecular cloning of GABAA receptor cDNAs from mammalian brain (6) has led to the identification of several closely related oL(1_3) and 13(1-3) subunit variants (7, 8) as well as two additional subunit classes, designated y(1,2) and 8(9,10). The deduced amino acid sequences of these subunits share several features (notably four hydrophobic predicted membrane-spanning domains)
22 citations
02 Mar 2007
TL;DR: Understanding how drugs work at synapses led to new drugs and advances in health care—a stunning record of achievement.
Abstract: The 130 years between Claude Bernard's demonstration that curare blocks neuromuscular transmission, but not nerve conduction or muscular contraction, and the cloning of receptor that binds the drug saw the emergence of neuropharmacology. Propelled by the staggering economic growth of the 19th Century and public support, the number of scientists and scientific institutions expanded enormously. It became clear that excitable cells interact though one-way junctions without cytoplasmic continuity: synapses. Drugs were discovered that block transmission at specific synapses or mimic the effects of nerve stimulation. Some thought that drugs bound to specific receptor sites, perhaps on arms of the huge molecule then believed to make up the protoplasm. The crucial step in elucidating the mechanism of transmission and revealing how the drugs act was Loewi's demonstration, in 1921, that stimulated nerves release a chemical that acts on the effector like nerve stimulation. Many concluded that synaptic transmission is chemical. Others argued that this could not be because transmission is so fast—it must be electrical. The argument was finally resolved in the 1950's when it was shown that the potential changes produced by presynaptic nerve stimulation reverse in sign at a set level of postsynaptic potential, demonstrating that the released transmitters open ion channels in the postsynaptic membrane. Transmission is fast because the transmitters bind, open an ion channel, and then are promptly released so the channel closes. These receptors are operated by the high local concentrations of transmitter produced by quanta1 release. Understanding how drugs work at synapses led to new drugs and advances in health care—a stunning record of achievement.
Keywords:
ion channels;
synaptic vesicles;
adrenergic transmitters;
amino acid transmitters;
curare;
neurons;
chemical transmission
9 citations
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References
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TL;DR: Using the fully sequenced 1300 nucleotide-long bovine preproenkephalin mRNA, it is established by sequencing that the method yields faithful full-length transcripts.
4,214 citations
Journal Article•
2,490 citations
01 Jan 1983
TL;DR: A Monumental Treatise...
Abstract: A Monumental Treatise... HANDBOOK OF NEUROCHEMISTRY Edited by Abel Lajtha, New York State Research Institute for Neurochemistry and Drug Addiction, Ward's Island, New York Three volumes of this treatise have already been published. Ultimately it will comprise seven volumes, presenting a comprehensive evaluation of the current chemical and biological literature on the nervous system and brain function. Volume 4: CONTROL MECHANISMS IN THE NERVOUS SYSTEM Investigates transmitters and their metabolism, enzymes presumably involved in transmission, and biological phenomena which are necessarily related to control. APPROX. 580 PAGES MARCH 1970 $35.00
1,231 citations
TL;DR: The whole primary structure of the γ-subunit precursor of the AChR deduced from the nucleotide sequence of the cloned cDNA is reported, suggesting that these polypeptides are oriented in a pseudosymmetric fashion across the membrane.
Abstract: The nicotinic acetylcholine receptor (AChR) from the electroplax of the ray Torpedo californica is composed of five subunits present in a molar stoichiometry of alpha 2 beta gamma delta (refs 1-3) and contains both the binding site for the neurotransmitter and the cation gating unit (reviewed in refs 4-6). We have recently elucidated the complete primary structures of the alpha-, beta- and delta-subunit precursors of the T. californica AChR by cloning and sequencing cDNAs for these polypeptides. Here, we report the whole primary structure of the gamma-subunit precursor of the AChR deduced from the nucleotide sequence of the cloned cDNA. Comparison of the amino acid sequences of the four subunits reveals marked homology among them. The close resemblance among the hydrophilicity profiles and predicted secondary structures of all the subunits suggests that these polypeptides are oriented in a pseudosymmetric fashion across the membrane. Each subunit contains four putative transmembrane segments that may be involved in the ionic channel. The transmembrane topology of the subunit molecules has also been inferred.
746 citations