Transport phenomena in a model membrane accompanying a conformational change: Transient processes in response to external stimuli

Summary A model membrane composed of a filter paper and dioleylphosphate was studied by applying various kinds of external stimuli. When the concentration in the external solution was varied successively, the physico-chemical properties of the membrane changed drastically at a certain valueC _t . The relationships between the electrical response and the external stimuli studied are as follows: (1) The membrane potential oscillates spontaneously in a spikelike fashion when the concentration of the external solution is suddenly changed. (2) The current through the membrane oscillates in spikelike fashion for a duration of about 50 msec when the constant external voltage, V larger than a certain value V _c , is applied across the membrane. (3) The electric resistance sharply decreases, and a kind of action potential similar to that observed in living tissues is produced when a short rectangular electric stimulus, whose magnitude is higher than a critical value V _p , is applied. (4) If a hydrostatic pressure difference across the membrane is applied with appropriate salt conditions, the value of the membrane potential varies with time, as in the case of (3). The observed changes in emf and electric resistance are discussed in connection with the conformational change of DOPH molecules in the membrane.     

Chemical specificity of short-chain fatty acid-induced electrogenic secretory response in the rat colonic mucosa

1. Luminal additions of normal short-chain fatty acids (SCFA: 3-6 carbons) increased transmural potential difference (PD: lumen negative) across rat everted colon in a dose-dependent manner. 2. The PD response to SCFA adapted rapidly and was not evoked by further cumulative addition of the same acid (self-adaptation) or different acids (cross-adaptation). 3. A broad range of SCFA derivatives were tested as potential stimulators of the PD response and cross-adaptation with propionate: a single carboxyl group and 3-6 carbon-chain were an absolute requirement for recognition. 4. These results suggest that SCFA-reception mechanism of the rat colonic mucosa has some sort of chemical specificity for stimulating electrogenic secretory response.     

A functional model of the wiring of the simple cells of visual cortex

A computer model of the simple cells in the mammalian visual cortex was constructed. The model cells received inputs from a great number of isopolar centre/surround cells assumed to be located in the lateral geniculate nucleus (LGN). The distribution of input to the model simple cells was either inhibitory/excitatory or inhibitory/excitatory/inhibitory. Such arrangements produced receptive fields containing four or five consecutively antagonistic subfields. Responses produced by the model cells to different types of stimuli (periodical as well as nonperiodical) were obtained and compared to responses of living cells reported from various laboratories under comparable stimulus conditions. In all the situations tested, the responses of the model cells corresponded qualitatively very well to those of living cells. It was seen that the same wiring mechanism was able to account for orientation selectivity, spatial frequency filtering, various phase relationships between stimulus and response, subfield orientational selectivity, and slight end-inhibition. Furthermore, the receptive fields of the model simple cells closely resemble Gabor functions.     

Direct measurement of translingual epithelial NaCl and KCl currents during the chorda tympani taste response.

We have measured the NaCl or KCl currents under voltage clamp across the dorsal lingual epithelium of the rat and simultaneously the response of the taste nerves. Under short-circuit conditions a NaCl stimulus evoked an inward current (first current) that coincided with excitation of the chorda tympani. This was followed by a slower inward current (second current) that matched the kinetics of taste nerve adaptation. The peak first current and the coincident neural response satisfied the same saturating NaCl concentration dependence. Both first and second currents were partially blocked by amiloride as were the phasic and tonic components of the neural response. The NaCl-evoked second current was completely blocked by ouabain. Investigation of the NaCl-evoked current and the neural response over a range of clamped voltages showed that inward negative potentials enhanced the inward current and the neural response to 0.3 M NaCl. Sufficiently high inward positive potentials reversed the current, and made the neural response independent of further changes in voltage. Therefore, one of the NaCl taste transduction mechanisms is voltage dependent while the other is voltage independent. A KCl stimulus also evoked an inward short-circuit current, but this and the neural response were not amiloride-sensitive. The data indicate that neural adaptation to a NaCl stimulus, but not a KCl stimulus, is mediated by cell Na/K pumps. A model is proposed in which the connection between the NaCl-evoked second current and cell repolarization is demonstrated.     

Characteristics of the water response across the dorsal epithelium of frog tongue

1. Dorsal epithelium of the frog tongue produced a change in potential difference across the tissue in response to removal of NaCl from the adapting Ringer solution on the mucosa. 2. The response was not caused by an osmotic decrease in the stimulus, and its profile was in many respects similar to that of the receptor potential in frog taste cells. 3. In conclusion, the response may influence or modify water reception in frogs.     

Über die Nachrichtenaufnahme durch biologische Receptoren

Summary The Hodgkin-Huxley theory of ion fluxes across membranes during excitation is extended to explain the graduated depolarisation (receptor potential) of sensory cell membranes. Electric circuit equivalents of living membranes are developed. Driving forces and velocity coefficients are represented by means of electric parameters. From this model active and passive ionic fluxes can be calculated quantitatively on the basis of transport equations derived from irreversible thermodynamics. Thus the circuit equivalent may be used as an analog computer. Electric receptor models allow a reproduction of all potential curves which have been derived in electrophysiological experiments on PD-receptors. The results obtained by the use of this model agree with the results obtained in biological experiments under various conditions of stimuli. The significance of solution compartments for intra-and extracellular ions in relation to the time functions of various conditions are discussed in detail. This models are of heuristic value in experimental research. In combination with neuron networks they can be used for the analysis of information theoretical problems.     

Opponent inhibition: a developmental model of layer 4 of the neocortical circuit.

We model the development of the functional circuit of layer 4 (the input-recipient layer) of cat primary visual cortex. The observed thalamocortical and intracortical circuitry codevelop under Hebb-like synaptic plasticity. Hebbian development yields opponent inhibition: inhibition evoked by stimuli anticorrelated with those that excite a cell. Strong opponent inhibition enables recognition of stimulus orientation in a manner invariant to stimulus contrast. These principles may apply to cortex more generally: Hebb-like plasticity can guide layer 4 of any piece of cortex to create opposition between anticorrelated stimulus pairs, and this enables recognition of specific stimulus patterns in a manner invariant to stimulus magnitude. Properties that are invariant across a cortical column are predicted to be those shared by opponent stimulus pairs; this contrasts with the common idea that a column represents cells with similar response properties.     

A kinetic model of the transient phase in the response of olfactory receptor neurons

A model is presented that predicts the instantaneous spike rate of an olfactory receptor neuron (ORN) in response to the quality and concentration of an odor stimulus. The model accounts for the chemical kinetics of ligand-receptor binding and activation processes, and implicitly the initiation of second messenger cascades that lead to depolarization and/or hyperpolarization of the ORN membrane. Both of these polarizing processes are included in the most general form of the model, as well as a process that restores the voltage to its negative resting state. The spike rate is assumed to be linearly proportional to the level of voltage depolarization above a critical negative voltage level. The model includes the simplifying assumption that activation of bound ligand-receptor complexes by G-proteins and other enabling molecules follows a Monod function that has the ratio of enabling molecules to bound unactivated ligand-receptor complexes as its argument. Parameters are selected that provide an excellent fit of the model to previously published empirical data on the response of cockroach ORNs to pulsed 1-hexanol stimuli. The sensitivity of model output to various model parameters is investigated and changes to parameters are discussed that would improve the ability of ORNs to follow rapidly pulsed stimuli.     

The flux-force relations across complex membranes with active transport

Equations are derived for the total material flux, and the total electric current flux, across a complex membrane system with active transport. The equations describe the fluxes as linear functions of forces across the system, and specifically of electrical potential, hydrostatic pressure, chemical potentials, and active transport rates. The equations can be simplified for experimental studies by making one or more of the forces equal to zero. The osmotic pressure difference across a membrane system is shown to be a function of the electrical potential and chemical potential differences and of the active transport rates. The transmembrane potential is shown to be the sum of a diffusion potential and an active transport potential. A simple equation is derived describing the current across a membrane as a linear function of the electrical potential and the active transport rate. Specific examples of the application of the equations to nerve membrane potentials are considered.     

Zigzagging and casting as a programmed response to wind-borne odour: a review

ABSTRACT. 'Counterturning' (meaning here the execution of a succession of alternating left and right turns) is the common feature in upwind zigzagging and cross-wind casting by flying insects manoeuvring towards a small source of wind-borne odour. Recent progress in understanding its control and function is discussed. Counterturning is internally controlled ('self-steered') in the limited sense that, once initiated by a chemical stimulus, it continues without further changes in the chemical input both in clean air and in a homogeneous cloud of odour. As a reaction it appears to be the kind of chemotaxis distinguished as longitudinal klinotaxis, for which the stimulus is a difference of chemical concentration detected over time along the insect's path, not across it. The new directions taken in response to the stimulus, being self-steered in the above sense, have no necessary relation to the direction of the chemical gradient that provided the stimulus but are influenced by the visual cues generated by wind drift. In wind, the counterturning programme is modulated by changes in the chemical input and simultaneously integrated with anemotaxis, but it can then continue in similar form after the wind has ceased. Unambiguous evidence for these conclusions is so far available only for certain flying male moths responding to sex pheromone. The primary function of counterturning, of all amplitudes and in both zigzagging and casting, appears to be the regaining of contact with an elusive scent.     

Reflex pressure response to the electric stimulation of different parts of the rat stomach

The role of the autonomic nervous system in the pressor response to the electrical stimulation of different gastric zones has been studied in rats. The stimulus was applied before and after the following interventions: bilateral vagotomy, ganglionic blockade, alpha-adrenergic receptor blockade and beta-adrenergic receptor blockade. After the ganglionic blockade no pressor responses to the electrical stimulus were observed. After the alpha-adrenergic blockade a lower pressor response was observed. A hypertensive response can be induced by mechanical, chemical or electrical stimulation of gastric receptors. It is concluded that the pressor reflex following the application of an electrical stimulus on different zones of the digestive tract is mediated by the sympathetic nervous system and that the efferent pathways are mainly alpha-adrenergic ones.     

Application of Statistical Thermodynamics to the Olfaction Mechanism

The application of the grand canonical ensemble in statisticalthermodynamics to the stimulus adsorption on the olfactory receptorsites, assuming some simplifying hypotheses, leads us to anexpression of the olfactory response R, which is a functionof various physico-chemical parameters involved in the olfactionmechanism, e.g. the stimulus concentration, the saturated vaporpressure, the power law exponent and the partition coefficient.This expression of R is in agreement with the olfactory responseof the Hill model, but is more explicit. Stevens' law and theolfactory threshold expression are easily deduced from R. Theexpression of the threshold we established from R enabled usto explain some empirical relations in the literature betweenthe parameters quoted above. The use of the grand canonicalensemble with the chemical potential notion gave us an interpretationof Stevens' law and a better understanding of the role of someparameters involved in the olfaction mechanism, such as saturatedvapor pressure and power law exponent. Chem. Senses 22: 67–75,1997.     

On Blair's theory of excitation and the role of internal energy sources

It is shown that Blair's theory of excitation is independent of, and consequently valid for, any possible relationship between the threshold and the magnitude of the stimulus. It is pointed out that if a dependence of threshold on stimulus is assumed, the concept of rheobase becomes meaningless. Consequently contrary to Blair's impression, the disagreement between his theory in its original form and the experimental data on the time of incipient excitation with constant stimulus (response time) cannot be explained by assuming a dependence of the threshold on the magnitude of the stimulus. It is shown that a modification of Blair's interpretation, obtained by taking into account effects of internal energy sources released by the stimulus, eliminates the disagreement mentioned above between theory and experiment. The role of such modification in connection with propagation of excitation is discussed.     

Vertical signal flow and oscillations in a three-layer model of the cortex

A model of vertical signal flow across a layered cortical structure is presented and analyzed. Neurons communicate through spikes, which evoke an excitatory or inhibitory postsynaptic potential (spike response model). The layers incorporate two anatomical features - dendritic and axonal arborization patterns and distance-dependent time delays. The vertical signal flow through the network is discussed for various stimulus conditions using two different, but typical, axonal arborization patterns. We find stationary as well as oscillatory response, but the oscillatory response may be restricted to a single layer. Confronted with conflicting stimuli the network separates the patterns through phase-shifted oscillations. We also discuss two hypothetical animals, to be called cat and mouse. These have different axonal arborizations, which give rise to a different oscillatory response (if any) of the various layers.     

Excitation of central nervous system neurons by nonuniform electric fields.

The goal of this study was to determine which neural elements are excited by microstimulation of the central nervous system. A cable model of a neuron including an axon, initial segment, axon hillock, soma, and simplified dendritic tree was used to study excitation with an extracellular point source electrode. The model reproduced a wide range of experimentally documented extracellular excitation patterns. The site of action potential initiation (API) was a function of the electrode position, stimulus duration, and stimulus polarity. The axon or initial segment was always the site of API at threshold. When the electrode was positioned near the cell body, the site of excitation was dependent on the stimulus amplitude. With the electrode in close proximity to the neuron, short-duration cathodic pulses produced lower thresholds with the electrode positioned over the axon than over the cell body, and long-duration stimuli produced opposite relative thresholds. This result was robust to alterations in either the maximum conductances or the intracellular resistivities of the model. The site of maximum depolarization was not always an accurate predictor of the site of API, and the temporal evolution of the changes in membrane potential played a strong role in determining the site of excitation.     

Epithelial responses to glycinamide and glycylglycinamide in the frog (Rana catesbeiana) tongue.

1. Open-circuit potential difference and short-circuit current across the frog tongue epithelium in response to glycinamide and glycylglycinamide were investigated. 2. Response to both of these amides were larger than the responses produced by glycine, glycylglycine and NaCl, and were independent of Na+ in the mucosal medium but dependent on H+ in the stimulus. 3. The relationships of the magnitudes of both response to the stimulus were similar to that in the taste nerve. 4. The results indicate that H+-dependent transport of these amides is related to taste reception in frogs.     

The flash-triggering action potential of the luminescent dinoflagellate Noctiluca

The action potential which elicits luminescence in Noctiluca is recorded from the flotation vacuole as a transient all-or-none hyperpolarization in response to either local or general application of inward (bath to vacuole) current. Experiments were performed to determine whether the unorthodox polarities of both the stimulus current and the potential response resulted from uncommon bioelectric mechanisms or from special morphological features of this species. The findings all indicate that the action potential belongs to the familiar class of responses which have their origin in voltage- and time-dependent selective increases in membrane permeability, and that morphological factors account for the observed deviations from normal behavior. Both the stimulus and the response have orthodox polarities provided the vacuole is designated as an "external" extracytoplasmic compartment. Differential recording between vacuole and cytoplasm showed that the action potential occurs across the vacuolar membrane, with the cytoplasmic potential, which at rest is negative with respect to the vacuole, overshooting zero and reversing sign to become transiently electropositive. The rising phase of the action potential therefore depends on active current flow through the vacuolar membrane from the vacuole into the cytoplasm. Propagation of the action potential over the subspherical cell from the locus of stimulation is thought to depend largely on the core conductor properties of the thin perivacuolar shell of cytoplasm which is bounded on its inner surface by the excitable membrane and on its outer surface by inexcitable membranes.