Bioenergetics of nerve excitation

The process of action potential production is analyzed in relation to the problem of energy transduction in the nerve. Describing the conditions required for the maintenance of excitability, the indispensability of divalent cations and the dispensability of univalent cations in the external medium are emphasized. Univalent cations with a strong tendency toward hydration enhance the action potential amplitude when added to the external Ca-salt solution. Experimental facts are described in consonance with the macromolecular interpretation of nerve excitation which postulates a transition of the negatively charged membrane macromolecules from a hydrophobic (resting) state to a hydrophilic (excited) state. Thermodynamic implications are discussed in relation to changes in enthalpy and volume accompanied by action potential production. Difficulties associated with analyses of excitation processes on a molecular basis are stressed.     

Quantum theory of nerve excitation

Based on quantum transitions of membrane dipoles, the four fundamental properties of nerve impulse are derived in this paper: the all-or-none response, the strength-duration relation, refractoriness and refractory period and frequency modulation. Furthermore, the theory offers a physical mechanism for nerve excitation similar to a two-level ammonia maser. It also implies non-threshold excitation at elevated temperatures. The role of trimethylamine ions near the surface of a phospholipid membrane is briefly discussed to indicate a possible connection between theory and reality.     

Molecular mechanisms of nerve excitation and conduction

In this paper we propose that the physical behavior of the electric dipoles at the membraneinterface is mainly responsible for the observed phenomena in nerve excitation and conduction. The underlying molecular mechanisms are conceived to be dipole reorientation, relaxation and flip-flops. It is suggested that quantum transitions of electric dipoles and a few first principles provide a real physical basis for the neural behavior as manifested macroscopically. This dipole theory gains a strong support from the most recent discoveries of negative fixed surface charge on axon membranes, infrared emission from stimulated nerve and the birefringence change which coincided with the action potential in squid axon. It can also offer an explanation for the heat production and absorption in excited nerves. A brief discussion will be given to the memory mechanism in terms of the field-dipole interaction during the RNA synthesis in nerve cells. Visiting the Research Institute of Electronics, Chiao-Tung University, Hsinchu, Formosa (Taiwan), September 1, 1968–June 1, 1969.     

A note on the excitation of nerve pathways

LetS denote the intensity of a stimulus, ν the frequency of discharge of a fiber, and ν _T the integral frequency of discharge of a nerve pathway. The relation between ν _T andS can be derived when the relation between ν andS, as well as the distribution function of the fiber thresholds are given. It is investigated under what conditions the functions ν _T (S) and ν(s) will be both of the same exponential form, and it is shown that this can happen only ifS exceeds the highest threshold of the pathway.     

Biophysics of mechanoreception

Several types of cells' skeletal, muscle, nerve, epithelia, and heart have been shown to contain ion channels which are sensitive to membrane tension. In chick skeletal muscle, the transduction persists in excised patches and involves no chemical messengers. Quantitative analysis of single channel records reveals that the sensitivity to stretch can be described by a linear four state model with three closed (C) and one open (O) state: (Formula: see text). Only the rate constant k12 is sensitive to tension (and membrane potential) following the law: k12 = kO12 exp/(theta T2 + alpha V) where theta is a constant describing the sensitivity to tension, T, and alpha is a constant describing the sensitivity to voltage, V, and kO12 is a constant. The form of the tension sensitivity can be accounted for by a model in which strain energy is used to gate the channel. Analysis of strain sensitivity, theta, indicates that the channel must concentrate energy from a large (ca. 500-nm diameter) area of membrane which suggests that the channel is in series with a component of the cytoskeleton. Treatment with cytochalasins suggests that actin is mechanically in parallel with the channel. When a channel with the above properties is incorporated into a simple model of mechanical transduction in hair cells, the resulting model is capable of explaining the kinetic features and the sensitivity found in the cochlear-vestibular system. The proposed gating mechanism of mechanical transduction appears to be general and can account for existing data on a variety of systems.     

Spectral analyses of absorption changes associated with nerve excitation in dye-stained crab nerve

Spectral characteristics of absorption changes associated with nerve excitation were studied with crab nerves stained with a homologous series of dyes, merocyanine-rhodanines and rhodanine oxonols. In these classes of dyes, the absorption changes which followed approximately the same time course as that of the action potential (fast responses) depended in a similar fashion on the wavelength and polarization of the incident light. In order to interpret those commonly observed dependencies, a mode of reorientation of the absorption oscillators of the dye molecules in the membrane matrix during nerve excitation was proposed. In addition to the fast changes mentioned above, slow responses which developed during and after the action potential were commonly observed with oxonols. The spectra of the slow changes differed from those of the fast ones, indicating a distinct mechanism on the response production. A possible mechanism of the production of fast responses was also discussed based on the proposed mode of reorientation of the absorption oscillators.     

Anodal excitation in the Hodgkin-Huxley nerve model.

Computations show that cathodal rheobase increases with temperature from 0 degrees C to 30 degrees C. Anodal rheobase (stimulation at the end of an indefinitely long anodal pulse) also increases with temperature, but goes to infinity at a critical temperature 17.13 degrees C, above which such excitation is impossible. For a stimulus consisting of any step change of current from I0 to I1, a threshold curve of I1 is plotted against I0. As the temperature increases, this curve rises. Its intersection with the horizontal axis, which determines the anodal rheobase, goes to infinity at the critical temperature. This phenomenon is caused by the saturation of the variables m, h, n for strongly hyperpolarized potentials, combined with the relative speeding up of the inhibitory process with increasing temperature. The threshold charge Q in an instantaneous anodal current pulse (of zero duration) goes to infinity at the same temperature, with a similar explanation in terms of threshold curves in the I1 vs. Q plane. The fact that the critical temperature for both cases is the same is generalized by the conjecture that for any anodal current waveform whatever, as its amplitude approaches infinity, the trajectory in the phase space following its cessation approaches the same limiting trajectory. This limiting trajectory changes from suprathreshold to subthreshold at the critical temperature.     

Study of changes in diacylglycerol content on nerve excitation

Rhythmic excitation of a rabbit myelin nerve increased diacylglycerol (DAG) content from 1.53 to 2.17 microg/mg lipids. Inhibition of phosphoinositide-specific phospholipase C decreased DAG content. This suggests involvement of this enzyme in processes accompanying rhythmic excitation. The increase in membrane potential of the nerve fiber (K+-depolarization) was accompanied by increase in DAG and phosphatidylinositol monophosphate and decrease in phosphatidylinositol triphosphate and phosphatidylinositol diphosphate content. Treatment of the nerve with DAG or a protein kinase C activator increased (45)Ca influx by 40%, whereas treatment with an inhibitor of this enzyme, polymyxin, inhibited this parameter by 34%. The role of phosphoinositides and protein kinase C in the regulation of Ca2+ transport during rhythmic excitation of the myelin nerve is discussed.