ABSTRACT
The electrical activity by which impulses are conducted along nerve and muscle fibers, is carried by Na-and K-ions moving across the excitable membranes due to increased ion permeability. -- A biochemical approach, initiated to elucidate the mechanism of the permeability changes, centered around the analysis of the properties and functions of the proteins, including enzymes, directly associated with the role of AcCh, in the excitable membrane. The results necessitated a fundamentally reformed concept of the role of AcCh. The four proteins specifically associated with the function of AcCh form a cycle which controls the rapid ion permeability changes of the membrane and permits the ion fluxes through dynamic gateways. A model has been elaborated that integrates biochemical, biophysical, and thermodynamic data; it permits the interpretation of many electrophysiological data in molecular terms. AcCh has basically the same function in conducting and synaptic parts of excitable membranes. The new concept has replaced the purely descriptive phenomenology of nerve impulse propagation by the analysis of the chemical mechanisms of nerve excitability and bioelectricity.
Subject(s)
Peripheral Nerves/physiology , Acetylcholine/physiology , Animals , Membranes , Mice , Models, Biological , Neural Conduction , Permeability , Potassium/metabolism , Sodium/metabolism , Synapses , Synaptic TransmissionABSTRACT
The paper recalls some fundamental notions, developed by Otto Meyerhof, which were used in the analysis of the transduction of chemical into mechanical energy during muscular contraction. These notions formed the basis of the approach to the analysis of the transduction of chemical into electrical energy, i.e., the very principle underlying nerve and muscle excitability and bioelectricity. Instrumental for this purpose was the use, since 1937, of electric organs of fish, a tissue highly specialized for bioelectrogenesis.
Subject(s)
Acetylcholine/metabolism , Electric Organ/metabolism , Membrane Potentials , Models, Biological , Action Potentials , Animals , Anura , Calcium/metabolism , Electrophorus , Mice , Neuromuscular Junction/ultrastructureABSTRACT
Although numerous experimental data have been accumulated in the various fields of research on bioelectricity, the mechanism of nerve excitability is still an unsolved problem. Many mechanistic interpretations of nerve behavior cover only a part of the facts, are thus selective and unsatisfactory. An attempt at an integral interpretation of basic data well-established by electrophysiological, biochemical, and biophysical investigations was inspired by the late Aharon Katchalsky and a first attempt had been made previously (Neumann et al., 1973). The present account is a further step toward a quantitative physiochemical theory of bioelectricity. We have further explored the previously introduced notion of a basic excitation unit in excitable membranes. This notion is of fundamental importance for modeling details of sub- and suprathreshold responses, such as threshold behavior and strength-duration curves, in terms of kinetic parameters for specific membrane processes. Our integral model of excitability is based on the original chemical hypothesis for the control of bioelectricity (Nachmansohn, 1959, 1971b). This specific approach includes some frequently ignored experimental facts on acetylcholine-processing proteins in excitable membranes. According to the integral model, acetylcholine ions are continuously processed through the basic excitation units within excitable membranes: axonal, presynaptic, and postsynaptic parts. Excitability, i.e., the generation and propagation of nerve impulses, is due to a cooperative increase in the rate of AcCh translocation through the cholinergic control system.
Subject(s)
Models, Neurological , Neurons/physiology , Acetylcholine/physiology , Acetylcholinesterase/metabolism , Action Potentials , Calcium/pharmacology , Choline O-Acetyltransferase/metabolism , Electric Stimulation , Hot Temperature , Mathematics , Membrane Potentials , Molecular Conformation/drug effects , Neural Conduction , Parasympathetic Nervous System/physiology , Proteins/metabolism , Refractory Period, Electrophysiological , Sensory Receptor Cells/physiology , Synaptic Membranes/physiologySubject(s)
Nerve Tissue Proteins/physiology , Neurons/physiology , Acetylcholinesterase/metabolism , Animals , Axons/drug effects , Axons/enzymology , Axons/physiology , Biological Transport , Calcium/metabolism , Carbamates/pharmacology , Choline/pharmacology , Eels , Electric Conductivity , Electric Organ/cytology , Electric Organ/physiology , Electric Stimulation , Histocytochemistry , Mathematics , Membrane Potentials , Membranes/enzymology , Microscopy, Electron , Models, Neurological , Neurons/cytology , Permeability , Time FactorsABSTRACT
A qualitatively consistent integral interpretation of biochemical, electrophysiological, and biophysical data on nerve activity is given in terms of a basic excitation unit. This operational term models a dynamically coupled assembly of membrane components accounting for graded and all-or-none responses upon stimulation. The analysis contains a series of suggestions linking controversial interpretations and is aimed at stimulation of experimental studies providing the basis for a quantitative integral theory of nerve excitation.
Subject(s)
Neurons/physiology , Acetylcholine/physiology , Action Potentials , Calcium/metabolism , Membrane Potentials , Models, Neurological , Neurons/metabolism , Receptors, CholinergicSubject(s)
Neurochemistry/history , Acetylcholinesterase , Acetyltransferases , Choline , Germany , History, 20th Century , Neural Conduction , Paris , Receptors, Drug , United StatesABSTRACT
Evidence has accumulated in recent years for the central role of proteins and enzymes in the function of cell membranes. In the chemical theory proposed for the generation of bioelectricity, i.e., for the control of the ion permeability changes of excitable membranes, the protein assembly associated with the action of acetylcholine plays an essential role. Support of the theory by recent protein studies in which the excitable membranes of the highly specialized electric tissue were used will be discussed. A scheme is presented indicating the possible sequence of chemical reactions that change ion permeability after excitation. A sequence of chemical events within the excitable membranes of the synaptic junctions, i.e., within the pre- and postsynaptic membranes, similar to that proposed for the conducting membranes, is presented in a second scheme as an alternative to the hypothesis of the role of acetylcholine as a transmitter between two cells.
Subject(s)
Cell Membrane/physiology , Neural Conduction , Acetylcholine/physiology , Acetylcholinesterase/physiology , Animals , Cell Membrane/enzymology , Cell Membrane Permeability , Eels , Electric Organ/enzymology , Electric Organ/physiology , Electrophysiology , Membrane Potentials , Microscopy, Electron , Receptors, Cholinergic , Synaptic TransmissionSubject(s)
Cell Membrane/enzymology , Membrane Potentials , Proteins , Animals , Cholinesterase Inhibitors , Crustacea , Isoflurophate/pharmacology , MolluscaABSTRACT
The photochromic compounds N-p-phenylazophenyl-N-phenylcarbamylcholine chloride and p-phenylazophenyltrimethylammonium chloride inhibit the carbamylcholine-produced depolarization of the excitable membrane of the monocellular electroplax preparation of Electrophorus. The trans isomer of each predominates in the light of a photoflood (420 mmu) lamp; they are stronger inhibitors than the cis isomers, which predominate under ultraviolet (320 mmu) irradiation. The potential difference across the excitable membrane may be photoregulated by exposing an electroplax in the presence of a solution of carbamylcholine and either of the two compounds to light of appropriate wavelengths, since light shifts the cis-trans equilibrium. The system may be considered as a model illustrating how one may link a cis-trans isomerization, the first step in the initiation of a visual impulse, with substantial changes (20-30 mv) in the potential difference across an excitable membrane.
Subject(s)
Acetylcholine/antagonists & inhibitors , Electric Organ/physiology , Animals , Azo Compounds , Carbachol , Eels , Electric Organ/drug effects , Light , Membrane Potentials , Models, Biological , Quaternary Ammonium Compounds , Receptors, Drug , Stereoisomerism , Ultraviolet RaysSubject(s)
Cholinesterase Inhibitors , Electric Organ/enzymology , Phosphates/pharmacology , Ambenonium Chloride/pharmacology , Animals , Cyprinidae , Echothiophate Iodide/pharmacology , Isoflurophate/pharmacology , Membrane Potentials , Nitrophenols/pharmacology , Phosphoric Acids/pharmacology , Pralidoxime Compounds/pharmacology , Receptors, Drug/drug effectsABSTRACT
Excitable membranes have the special ability of changing rapidly and reversibly their permeability to ions, thereby controlling the ion movements that carry the electric currents propagating nerve impulses. Acetylcholine (ACh) is the specific signal which is released by excitation and is recognized by a specific protein, the ACh-receptor; it induces a conformational change, triggering off a sequence of reactions resulting in increased permeability. The hydrolysis of ACh by ACh-esterase restores the barrier to ions. The enzymes hydrolyzing and forming ACh and the receptor protein are present in the various types of excitable membranes. Properties of the two proteins directly associated with electrical activity, receptor and esterase, will be described in this and subsequent lectures. ACh-esterase has been shown to be located within the excitable membranes. Potent enzyme inhibitors block electrical activity demonstrating the essential role in this function. The enzyme has been recently crystallized and some protein properties will be described. The monocellular electroplax preparation offers a uniquely favorable material for analyzing the properties of the ACh-receptor and its relation to function. The essential role of the receptor in electrical activity has been demonstrated with specific receptor inhibitors. Recent data show the basically similar role of ACh in the axonal and junctional membranes; the differences of electrical events and pharmacological actions are due to variations of shape, structural organization, and environment.