Nerve excitability: transition from descriptive phenomenology to chemical analysis of mechanisms.

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.

Transduction of chemical into electrical energy.

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.

Nerve excitability--toward an integrating concept.

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.

An attempt at an integral interpretation of nerve excitability.

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.

Chemical events in conducting and synaptic membranes during electrical activity.

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.

Photoregulation of biological activity by photochromic reagents. 3. Photoregulation of bioelectricity by acetylcholine receptor inhibitors.

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.

Proteins of excitable membranes.

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.

Cholinesterase activity per unit surface area of conducting membranes.

According to theory, the action of acetylcholine (ACh) and ACh-esterase is essential for the permeability changes of excitable membranes during activity. It is, therefore, pertinent to know the activity of ACh-esterase per unit axonal surface area instead of per gram nerve, as it has been measured in the past. Such information has now been obtained with the newly developed microgasometric technique using a magnetic diver.