Electrical properties of skeletal muscle fibres of the flour moth larva Ephestia kuehniella

The electrical properties of the ventral longitudinal muscle fibres in the flour moth larva Ephestia kuehniella were investigated at rest and during electrical activity. The membrane resting potential was only partially dependent on the K-concentration gradient across the muscle membrane. The electrical constants λ, τ, R_m, R_i, and C_m were determined according to the equations for ‘short cables’ (Table 1). Current-voltage relationships of the muscle membrane were measured: they revealed anomalous as well as delayed rectification of the membrane. Stimulation of the muscle fibres with intracellular current pulses elicited graded action potentials in most fibres; in some fibres ‘all-or-none’ action potentials were generated. In contrast to graded action potentials these ‘all-or-none’ action potentials were propagated without decrement along the muscle fibre. Indirect stimulation of the muscle fibres resulted in large excitatory junction potentials which generally gave rise to action potentials.     

An Example of Information Retention in Rabbit Ventricular Muscle Fibres

The preparation was stimulated externally and transmembrane action potentials were recorded with intracellular microelectrodes. The relationship between the area of the first action potential after a pause in stimulation and the duration of the pause was examined. It was found that the area retained its dependence on the pattern of stimulation prior to the pause. These experiments confirm one of the predictions of a mathematical model (Gibbs et al., 1963) which describes the relationship between the area of action potentials and the pattern of stimulation.     

Reinnervation of adult muscle in organ culture restores tetrodotoxin sensitivity in the absence of electrical activity.

Strips of denervated adult mouse diaphragm muscle maintained in organ culture were reinnervated by nerve processes growing out from explants of embryonic mouse spinal cord. In vivo, following denervation, the action potential loses its sensitivity to tetrodotoxin; this sensitivity is regained upon reinnervation. Similarly, action potentials in cultured muscle fibres were insensitive to tetrodotoxin, and sensitivity was restored in muscle fibres that became reinnervated in vitro. Tetrodotoxin sensitivity was also restored in cultured muscle fibres reinnervated in the continuous presence of d-tubocurarine, but it was not induced by 4 days of direct electrical stimulation of noninnervated muscles. We conclude that developing nerve terminals can exert a trophic action on adult muscle fibres that is independent of electrical activity in the muscle.     

Characterization of the neurotoxic constituents of Conus geographus (L) venom

The crude venom of the marine gastropod Conus geographus (L) has been separated into three lethal constituents and their actions at the mammalian neuromuscular junction examined.Chromatography of the venom of Sephadex G-50 gave one toxic fraction, which was resolved by ion exchange chromatography on SP-Sephadex into three toxic components. These components were individually purified by diafiltration and Sephadex G-15 chromatography to give Toxins I,II and III. Toxins I and II in concentrations greater than 5 ug/ml reduced the amplitude of end-plate potentials and miniature end-plate potentials; Toxin I also blocked the depolarization of muscle fibres produced by carbachol; neither toxin affected the generation of action potentials in muscle fibres. Toxin III in concentrations greater than 5 ug/ml rapidly and reversibly blocked the generation of action potentials in muscle fibres; it had no effect on resting membrane potential nor on the amplitude of epps or mepps. It also slowly blocked the compound action potential recorded from isolated sciatic nerves but this was not reversible in the experiments. The rate at which this toxin blocked action potentials was increased by stimulation of the preparation. It is suggested that Toxin III acts by blocking the inward movement of sodium during activity. Toxin III appeared to be a nonadeca or eicosa peptide possibly having a cystine residue in the N-terminal position.     

哺乳动物不活动化肌纤维的动作电位

用河豚毒素(TTX)慢性阻断大鼠坐骨神经的冲动传导,使后肢不活动,经过不同时间(最长7d)后离体观察了快肌伸趾长肌(EDL)和慢肌比目鱼肌(SOL)肌纤维终板区的诱发动作电位。我们发现在不活动期间动作电位超射和上升速率逐步下降,并从第4天起部分肌纤维能在含有1×10~(-7)g/ml TTX的溶液中被诱发产生动作电位(称抗TTX动作电位),待至第7天时全部SOL肌纤维和90％的EDL肌纤维都能被诱发出抗TTX动作电位。与去神经肌纤维相比,不仅抗TTX动作电位出现较晚,并且其超射和上升速率较低。在去掉TTX阻断使肌肉恢复活动后,动作电位超射和上升速率渐趋恢复,抗TTX动作电位逐渐消失。无论是动作电位的恢复还是抗TTX动作电位的消失,EDL肌纤维均快于SOL肌纤维。本文还讨论了不活动化使肌纤维动作电位变化以及快、慢肌差别的可能原因。     

Action potentials and ionic currents through paranodally demyelinated human motor nerve fibres: computer simulations

 The relationship between the changes in the passive paranodal properties of the myelinated human motor nerve fibres and the conduction abnormalities obtained is examined on the basis of a double-cable model. Simulated systematic demyelination (all paranodal regions uniformly affected) and focal demyelination (paranodal regions at each end of a single internode affected) of the fibres are defined as a reduction of the paranodal seal resistance. By increasing the degree of demyelination, the kinetics of the action potentials and ionic currents in different segments of the fibres are explored. The altered paranodal seal resistance is found to be a factor impeding the invasion of the demyelinated regions by an action potential. We established that the conduction along the most severely demyelinated fibres (i.e. in the case of systematically demyelinated fibres) is more affected than along the focally demyelinated fibres. Received: 8 July 1996/Accepted in revised form: 13 December 1996     

A three-state model for inactivation of sodium permeability

The inactivation of Na⁺ permeability in single myelinated motor nerve fibres of Rana esculenta was investigated under voltage and current clamp conditions at 20°C in Ringer's solution and under blocked K⁺ currents. Development of inactivation and its recovery was described by two potential-dependent time constants: The smaller time constant followed the usual bell-shaped function of membrane potential, whereas the larger one was monotone-increasing with more negative potentials. Several three-state models for inactivation were investigated. The experiments could best be approximated by a model with two open and one closed state for inactivation following: open ? closed ? open. Rate constants were determined for all transitions shown from the voltage clamp experiments. The action potentials computed by means of the proposed model were in good agreement with those measured, both in Ringer's solution and under blocked K⁺ current conditions.     

Analysis of the peak-to-peak ratio of extracellular potentials in the proximity of excitable fibres

In a previous work we studied the ratio between the amplitudes of the second and first phases (which we call PPR, after peak-to-peak ratio) of the single fibre action potential (SFAP) for a collection of fibrillation potentials (FPs) extracted from two pathological muscles. These FPs showed a wider PPR range than the Dimitrov–Dimitrova (D–D) convolutional model could provide. We proposed a modification of the D–D intracellular action potential (IAP) in order to obtain a range of PPRs comparable to that observed in our FPs. This paper extends that study to a large number of SFAPs extracted from the tibialis anterior muscle of normal subjects. The estimation of the average PPR range of non-diseased muscles in non-fatigued conditions is important since it can be used as a reference to establish a comparison with PPR ranges from muscles suffering some disorder or from fibres that are fatigued. Other aspects of the PPR, as its sensitivity with volume conductor parameters or to what extent changes in the SFAP PPR reflects changes in IAP spatial profile are also examined. We found that the PPR of experimental SFAPs ranges from 0.3 to 2.5 in all subjects and that all PPR histograms contain a well-defined single peak around the PPR value 1.0.     

Experimental studies upon a bundle of tonic fibres in the locust extensor tibialis muscle

The bundle of tonic fibres situated at the proximal end of the locust metathoracic extensor tibialis muscle is innervated by the dorsal unpaired median neurone (DUMETi) as well as by the slow excitatory (SETi)) and common inhibitor (CI) neurones. It is not innervated by the fast excitatory neurone (FETi).These fibres contract spontaneously and rhythmically. The myogenic rhythm can be modified by neural stimulation.Spontaneous slow depolarizing potentials resembling the pacemaker potentials of insect cardiac muscle were demonstrated in these fibres.The actions of glutamate on the tonic muscle fibres are not compatible with its being a specific excitatory transmitter. Glutamate can stimulate weak contractions of the muscle, but this action is inhibited when chloride ions are removed from the saline.10^?6 M Octapamine hyperpolarizes the tonic fibre membrane. Octopamine, GABA and glutamate all inhibit the myogenic contractions and reduce the force of the neurally evoked contractions.The tonic muscle is very responsive to proctolin. At 5 × 10^?11 M proctolin enhances the force and increases the frequency of myogenic contractions. At 10^?9 M it depolarizes the muscle membrane potential, and at that and higher concentrations it causes the muscle to contract. At 2 × 10^?7 M proctolin induces contractures which resemble those evoked by sustained high-frequency neural stimulation. Iontophoretic experiments show that proctolin receptors occur at localized sites on the tonic fibre membrane.     

Receptor Response in Venus''s Fly-Trap

The insect-trapping movement of the plant Dionaea muscipula (Venus's fly-trap) is mediated by the stimulation of mechanosensory hairs located on the surface of the trap. It is known that stimulation of the hairs is followed by action potentials which are propagated over the surface of the trap. It has been reported that action potentials always precede trap closure. The occurrence of non-propagated receptor potentials is reported here. Receptor potentials always precede the action potentials. The receptor potential appears to couple the mechanical stimulation step to the action potential step of the preying sequence. Receptor potentials elicited by mechanical stimulation of a sensory hair were measured by using the hair as an integral part of the current-measuring path. The tip of the hair was cut off exposing the medullary tissue; this provided a natural extension of the measuring electrode into the receptor region at the base of the hair. A measuring pipette electrode was slipped over the cut tip of the hair. Positive and negative receptor potentials were measured. Evidence is presented which supports the hypothesis that the positive and negative receptor potentials originate from independent sources. An analysis is made of (a) the relation of the parameters of mechanical stimuli to the magnitude of the receptor potential, and (b) the relation of the receptor potentials to the action potential. The hypothesis that the positive receptor potential is the generator of the action potential is consistent with these data.     

A unified model for two modes of bursting in GnRH neurons

Gonadotropin-releasing hormone (GnRH) neurons exhibit at least two intrinsic modes of action potential burst firing, referred to as parabolic and irregular bursting. Parabolic bursting is characterized by a slow wave in membrane potential that can underlie periodic clusters of action potentials with increased interspike interval at the beginning and at the end of each cluster. Irregular bursting is characterized by clusters of action potentials that are separated by varying durations of interburst intervals and a relatively stable baseline potential. Based on recent studies of isolated ionic currents, a stochastic Hodgkin-Huxley (HH)-like model for the GnRH neuron is developed to reproduce each mode of burst firing with an appropriate set of conductances. Model outcomes for bursting are in agreement with the experimental recordings in terms of interburst interval, interspike interval, active phase duration, and other quantitative properties specific to each mode of bursting. The model also shows similar outcomes in membrane potential to those seen experimentally when tetrodotoxin (TTX) is used to block action potentials during bursting, and when estradiol transitions cells exhibiting slow oscillations to irregular bursting mode in vitro. Based on the parameter values used to reproduce each mode of bursting, the model suggests that GnRH neurons can switch between the two through changes in the maximum conductance of certain ionic currents, notably the slow inward Ca²⁺ current I _s, and the Ca²⁺ -activated K⁺ current I _KCa. Bifurcation analysis of the model shows that both modes of bursting are similar from a dynamical systems perspective despite differences in burst characteristics.     

Spatial analysis of motor unit potentials of the rat medial gastrocnemius

The spatial analysis of the potentials of single motor units of the rat medial gastrocnemius muscle evoked by stimulation of the fibres of split ventral roots was carried out with a bipolar electrode moving in the direction perpendicular to the longitudinal axis of the muscle fibres. During this movement of the electrode a variability was observed in the time of the biphasic potential from its maximum to minimum, and in the peak-to-peak amplitude of these potentials. The potentials recorded outside the territory of the motor unit had a lower amplitude in relation to the potentials from the territory of the unit. This made localization of the motor unit on the cross-section of the muscle possible. Differences in the duration of the potential from maximal to minimal amplitude (maximum-minimum amplitude time--M-MAT) of each investigated motor unit from successive recording sites reflected the number of fibres contributing to the action potential and the distance of the recording surface of the electrode from the zone of the motor end-plates of this motor unit. The greatest diameter of the territory of the observed motor units reached 2.5 mm.     

Electrical Properties of the Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

In the Squilla heart ganglion, the pacemaker is located in the rostral group of cells. After spontaneous firing ceased, the electrophysiological properties of these cells were examined with intracellular electrodes. Cells respond to electrical stimuli with all-or-none action potentials. Direct stimulation by strong currents decreases the size of action potentials. Comparison with action potentials caused by axonal stimulation and analysis of time relations indicate that with stronger currents the soma membrane is directly stimulated whereas with weaker currents the impulse first arises in the axon and then invades the soma. Spikes evoked in a neuron spread into all other neurons. Adjacent cells are interconnected by electrotonic connections. Histologically axons are tied with the side-junction. B spikes of adjacent cells are blocked simultaneously by hyperpolarization or by repetitive stimulation. Experiments show that under such circumstances the B spike is not directly elicited from the A spike but is evoked by invasion of an impulse or electrotonic potential from adjacent cells. On rostral stimulation a small prepotential precedes the main spike. It is interpreted as an action potential from dendrites.     

Analysis of the relationship between the rise-time and the amplitude of single-fibre potentials in human muscles

Using the core-conductor theory, a single fibre action potential (SFAP) can be expressed as the convolution of a biolectrical source and a weight function. In the Dimitrov–Dimitrova (D–D) SFAP convolutional model, the first temporal derivative of the intracellular action potential (IAP) is used as the source. The present work evaluates the relationship between the SFAP peak-to-peak amplitude (V_pp) and peak-to-peak interval (rise-time, RT) at different fibre-to-electrode distances using simulated signals obtained by the D–D model as well as real recordings. With a single fibre electrode, we recorded 63 sets of consecutive SFAPs from the m. tibialis anterior of four normal subjects. The needle was intentionally moved whilst recording each SFAP set. We used the observed changes in RT and V_pp within each SFAP set as a point of reference with which to evaluate how closely the relationship between RT and V_pp provided by the D–D model reflects real data. We found that half of the recorded SFAP sets had rise-times higher than those generated by the D–D model. We also showed the influence of the IAP spatial length on the sensitivity of RT and V_pp with radial distance. The study reveals some inaccuracies in simulated SFAPs whose origin might be related to the assumptions made in the core-conductor theory.     

SEX HORMONE STUDIES—The Effects on the Cellular Membrane Potentials and Contractility of lsolated Rat Atrium

The effects of estradiol, testosterone and progesterone on the electrical and mechanical characteristics of rat atria were determined. Cellular membrane potentials were obtained with microelectrodes and the contractility recorded from a sensitive strain gauge. All three steroids at concentrations near 10⁻⁵ M produced characteristic changes in the membrane potentials, the most striking effect being a pronounced slowing of the depolarization of the action potential, without simultaneously reducing the magnitudes of the resting or action potentials. As a result, there was slower impulse conduction in the atria, a lengthening of the action potential and a consequent increase in the refractory period. The repolarization rate was slowed. These changes are due to effects on the transmembrane fluxes of Na⁺ and K⁺, a decrease in permeability being assumed.These effects are similar to those produced by the standard antiarrhythmic drugs, such as quinidine; and these steroids, particularly testosterone, have been found to be potent in the prevention and abolishment of atrial arrhythmias, both in vitro and in vivo. The steroids also block the effects of acetylcholine on the atria and this may play a role in the reduction in excitability and automaticity.Testosterone, but not estradiol nor progesterone, exerts a temporary stimulation of the atrial contractility, which is not due to any effect on the membrane, but is related in some manner more directly to the contractile systems.     

Supersensitivity to ACh in muscles after prolonged nerve block.

Sciatic nerves of rats and tibial nerves of rabbits were kept anaesthetized in situ for periods of 3-11 days by applying silastic cuffs containing lidocaine base or marcaine hydrochloride. To insure a more uniform release of the rapidly diffusing lidocaine base, the drug was contained in compartments at some distance from the nerve and the cuffs were covered with polystyrene. The completeness of anaesthesia and the functional state of the nerve were tested by stimulating the exposed nerves proximal and distal to the cuff and by observing the behaviour of the muscle prior to killing the animals. The ACh sensitivity was tested by electrophoretic application of ACh from micropipettes and by recording the results changes of the resting membrane potential in individual muscle fibres. The ACh sensitivity was found to be present in the extrajunctional area of all muscle fibres including those displaying miniature end-plate potentials. These was no difference between the behaviour of muscles from rats and rabbits and between the action of lidocaine base and marcaine hydrochloride. Previous reports on the absence of extrajunctional ACh sensitivity in muscles of rabbits whose nerves had been treated by lidocaine base were explained by a relatively rapid loss of the drug from the usual type of nerve cuffs (more than 70% of the drug lost in one day), permitting a premature recovery of the nerves from anaesthesia.     

A simple vector implementation of the Laplace-transformed cable equations in passive dendritic trees

Transient potentials in dendritic trees can be calculated by approximating the dendrite by a set of connected cylinders. The profiles for the currents and potentials in the whole system can then be obtained by imposing the proper boundary conditions and calculating these profiles along each individual cylinder. An elegant implementation of this method has been described by Holmes (1986), and is based on the Laplace transform of the cable equation. By calculating the currents and potentials only at the ends of the cylinders, the whole system of connected cylinders can be described by a set of n equations, where n denotes the number of internal and external nodes (points of connection and endpoints of the cylinders). The present study shows that the set of equations can be formulated by a simple vector equation which is essentially a generalization of Ohm's law for the whole system. The current and potential n-vectors are coupled by a n × n conductance matrix whose structure immediately reflects the connectivity pattern of the connected cylinders. The vector equation accounts for conductances, associated with driving potentials, which may be local or distributed over the membrane. It is shown that the vector equation can easily be adapted for the calculation of transients over a period in which stepwise changes in system parameters have occurred. In this adaptation it is assumed that the initial conditions for the potential profiles at the start of a new period after a stepwise change can be approximated by steady-state solutions. The vector representation of the Laplace-transformed equations is attractive because of its simplicity and because the structure of the conductance matrix directly corresponds to the connectivity pattern of the dendritic tree. Therefore it will facilitate the automatic generation of the equations once the geometry of the branching structure is known.     

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.     

Synaptic effects elicited in the Retzius cells of the leech Hirudo medicinalis by stimulation of the segmental roots

Electrical stimulation of the segmental roots of each ganglion of Hirudo medicinalis, elicits in both Retzius' cells inhibitory and excitatory effects. The IPSP and EPSP are chemical in nature, being dependent on the membrane potential, and suppressed by high Mg++. Selective inactivation of one RC shows that the responses of the contralateral RC are not due to electrotonic coupling between the two cells, but to synaptic actions impinging upon the membrane of both RCs. The two synaptic potentials appear to be mediated by two set of fibres with a different threshold to electrical stimulation. Their actions on the RCs appear to be polysynaptic on the basis of central latency. Simultaneous stimulation of two roots shows evidence for occlusion for IPSP and summation for EPSP, confirming the polysynaptic nature of the effects. The possible functional significance of the inhibitory and excitatory pathways, is discussed.     

Influence of the muscle fibre end geometry on the extracellular potentials

Intra- and extracellular action potentials of isolated frog muscle fibres were recorded at different distances to the end of the fibre. The first and second time derivatives of the intracellular action potentials were also recorded. The intracellular action potentials and their first and second time derivatives were almost the same regardless of the place of recording. With the decrease in the axial distance to the end the extracellular action potentials changed gradually in a complicated manner from a shape similar to the second time derivative into a shape similar to the first time derivative. Extracellular potentials, having two negative maxima, were recorded over the terminal taper part of the fibres.These alterations were simulated by a mathematical model. It was shown that the changes in the shape of the extracellular action potentials around the end of the fibres were mainly due to the existence of the fibre end though a better correspondence of the experimentally recorded and the calculated extracellular action potentials was obtained when the morphology of the fibre end was taken into consideration.