The electric activity of the motor end-plate

At the nerve-muscle junction, a specific process occurs which is not found during the propagation of impulses along nerve or muscle fibres; the nerve impulse causes acetylcholine (Ach) to be released from the motor nerve endings, and this substance depolarizes the end-plate surface of the muscle fibre by a specific chemical reaction. The transient local depolarization of the muscle fibre which is so produced has been called the end-plate potential (e.p.p.). The e.p.p., then, unlike the nerve or muscle impulse, is not itself produced by electric stimulation (direct spread of electric current from nerve to muscle has, in fact, never been demonstrated and appears to be indetectably small). On the other hand, the e.p.p. electrically stimulates the surrounding region of the muscle fibre, and so gives rise to the propagation of a new impulse.

External micro-electrodes were used to stimulate non-myelinated motor nerve terminals and to record pre- and post-synaptic responses at the neuromuscular junction of the frog. The synaptic terminals of the motor axon are electrically excitable. Antidromic nerve impulses can be set up by local stimulation of terminals along the greater part of their length. Presynaptic spikes can be recorded from the non-myelinated terminal parts of motor axons. As the impulse proceeds towards the tip of the terminal branch, the shape of the spike changes from a predominantly negative to a predominantly positive-going wave. Similar changes occur in muscle fibres near their tendon junctions, and can be attributed to the special local-circuit conditions at the ‘closed end’ of a fibre. The velocity of impulse propagation in motor nerve endings was determined by three different methods: ( a ) from the latency of antidromic nerve spikes elicited at different points along terminals, ( b ) from two-point recording of spikes along a terminal, ( c ) from the differential latency of focal end-plate potentials recorded at two spots of a myoneural junction. The average velocity obtained by these methods was approximately 0.3 m/s at 20 °C. Extracellular muscle fibre spikes recorded at junctional spots showed no significant differences from those recorded elsewhere, provided the spikes were initiated by direct stimulation and did not coincide with transmitter action. Direct current polarization produces a graded increase in frequency of miniature end-plate potentials when the endings are being depolarized, and sudden high-frequency bursts during excessive hyperpolarization. External two-point recording shows that these bursts arise independently at different spots of the synaptic terminals.


1966 ◽  
Vol 11 (1_suppl) ◽  
pp. 67-77
Author(s):  
J. Impastato David

Familiarity with certain physiologic and biochemical reactions and factors of succinylcholine (SCh) in man is helpful in safely administering SCh in convulsive therapy and anesthesiology. These reactions and factors are: 1) the natural variations in the titer of butyrylcholinesterase (BChE) in the plasma, 2) the interactions between SCh with BChE, 3) the action of SCh in the congenital absence of BChE, 4) understanding of the mechanism of transmission of the nerve impulse, 5) the action of succinylcholine at the motor end plate. Discussion of the above reactions and factors are presented. Two physiologic tests are described. These are the 3 mg SCh test dose and the tendon reflex test. The proper application of these two tests make possible the safest use of succinylcholine in convulsive therapy, as well as in other fields of medicine.


A micromethod is described by which depolarizing and inhibiting drugs can be applied, ionophoretically, from a common ‘point source’ to sensitive regions of a motor end-plate. The effects of the drugs on the membrane potential of a single end-plate are recorded, in the frog’s sartorius muscle. The antagonism between d -tubocurarine ( DTC ) and acetylcholine (or carbachol) is studied with this method. Close-range application of small quantities of the depolarizing agents (of the order of several times 10 -11 coulombs, or 10 -16 m) sets up transient potential changes of several millivolts amplitude. Application of a somewhat larger quantity of DTC (about 4 x 10 -10 C) produces a transient 50 % inhibition of the acetylcholine (or carbachol) potential. Curare does not alter the resting potential, nor the resistance or capacity of the end-plate or muscle fibre, but specifically interferes with the chemo-receptor properties of the end-plate. The inhibitory effect of DTC is obtained only with external application, but not with intracellular application from the inside of the muscle fibre. The decay of the inhibitory action of DTC is slow compared with the subsidence of the depolarization produced by acetylcholine or carbachol. The reason for this difference in time course is examined; it is probably due to relatively slow dissociation of the curare-receptor complex. Procaine in close-range, short-time application is as potent an inhibitor of acetylcholine action as DTC . The procaine effect subsides, however, much more rapidly than the action of curare.


Nature ◽  
1965 ◽  
Vol 206 (4984) ◽  
pp. 629-630 ◽  
Author(s):  
G. ROSSI ◽  
G. CORTESINA

1. The puffer fish poison, tetrodotoxin ( T . T .) was applied to eliminate impulse propagation in nerve and muscle fibre, and the physiological properties of the neuromuscular junction were studied under this condition. 2. Spontaneous miniature end-plate potentials of normal frequency and amplitude were recorded in the T . T .-paralysed muscle. 3. Depolarization of motor nerve endings by locally applied current still produces the usual increase in the frequency of miniature end-plate potentials (e. p. ps). 4. When brief current pulses are applied to the nerve endings e. p. ps can be evoked, whose size varies with the intensity of the current. The responses are composed, like normal e. p. ps, of a statistically varying number of miniature potentials. The response fails when calcium is removed from the bath. 5. When two identical pulses are applied at varying intervals, facilitation of the second e. p. p. occurs, similar to that observed normally with pairs of nerve impulses. 6. It is concluded that tetrodotoxin while blocking electric excitation in nerve and muscle does not interfere with the release of acetylcholine from nerve endings nor with its local action on the muscle fibre.


Interaction between different choline derivatives has been studied by applying them simultaneously to a motor end-plate and recording the resulting changes in the membrane potential of the muscle fibre. Choline potentiates the depolarizing effect of acetylcholine ( Ach ) when applied in normal Ringer. Decamethonium has a ‘diphasic’ action, initial depression of the Ach effect being followed by more prolonged potentiation. When these experiments are made after treating the muscle with an esterase inhibitor (prostigmine 10 -6 w/v), the potentiation of the Ach effect, by decamethonium or choline, is absent and replaced by simple ‘curare-like’ inhibition. When decamethonium is allowed to interact with a rapidly acting stable ester (carbaminoylcholine or succinylcholine), it produces simple 'curare-like’ inhibition. The triple effects of choline and decamethonium, i. e. (i) weak depolarization, (ii) potentiation of Ach in normal Ringer solution, (iii) inhibition of Ach in the presence of prostigmine, can be explained by competitive reactions between the drugs and receptor as well as Ach -esterase molecules. It is suggested that the first step in a depolarizing end-plate reaction is the formation of an intermediate, inactive, compound between drug and receptor.


1. The structure and innervation of muscle spindles from normal, de-afferented and de-efferented muscles of the cat hind limb were studied. The spindles were either completely isolated by microdissection, or were serially sectioned transversely. 2. All spindles contain two distinct types of intrafusal muscle fibre, ‘nuclear bag fibres’ and ‘nuclear chain fibres’, which differ in structure and innervation. 3. Nuclear bag muscle fibres, usually two per spindle, are less than half the diameter of extrafusal fibres, and each contains numerous large nuclei packed together in the equatorial region of the spindle. Nuclear bag fibres practically never branch. The fibres contain numerous myofibrils uniformly distributed in cross-sections, and relatively little sarcoplasm; they atrophy very slowly after the ventral spinal roots are cut. Several small motor nerve fibres (y, fibres) enter each spindle and terminate in a number of discrete motor end-plates on the nuclear bag muscle fibres. These y x end-plates lie in a group at each spindle pole and long lengths of nuclear bag fibre are free of motor innervation. 4. Nuclear chain muscle fibres, usually four per spindle, are about half the length and diameter of nuclear bag fibres in spindles in the leg muscles. The nuclear chain fibres in spindles from the small muscles of the foot may, however, equal the nuclear bag fibres in length, and in diameter beyond the ends of the lymph space. Each nuclear chain fibre contains a single row of central nuclei in the equatorial region; the fibres occasionally branch, but often none of them do so. They contain fewer myofibrils per unit area, irregular in size and distribution, and relatively more sarcoplasm, than nuclear bag fibres. Nuclear chain fibres atrophy nearly as rapidly as extrafusal fibres after the ventral roots are cut. A number of very fine motor nerve fibres fibres) enter each spindle and terminate in a network of fine axons and small nerve endings (the network’) situated on the nuclear chain muscle fibres in most regions other than the nuclear region. 5. All spindles receive both y 1 xand y 2 innervation, fibres forming slightly more than half of the total number of motor fibres which varies from seven in simple spindles in phasic muscles to twenty-five in the most complex spindles in tonic muscles. Both y 1 and y 2 fibres remain intact after dorsal root transection and degenerate following ventral root transection. The histological evidence supports the view that the yj and y2 nerve fibres at the spindles are derived from two types of stem fibre, neither of which belongs to the a group. 6. Each spindle has one primary sensory nerve ending, supplied by one group 1 a afferent nerve fibre, and from zero to five secondary sensory nerve endings, each supplied by one group II afferent nerve fibre. The primary sensory terminations lie on both nuclear bag and nuclear chain muscle fibres. The secondary sensory terminations lie predominantly on the nuclear chain muscle fibres. In spindles with several secondary sensory endings, their terminations may lie on the same region of nuclear chain fibres as motor endings of the y 2 network. 7. In general, spindles in tonic muscles have more secondary sensory endings and motor nerve fibres and endings than those in other muscles. Nuclear chain intrafusal fibres are probably functionally ‘slower’ than nuclear bag intrafusal fibres, while both types are ‘slower’ than extrafusal fibres. Both nuclear chain fibres and nuclear bag fibres, however, probably show a gradation in activity related to the nature of the muscle in which they lie. The reader is advised to study figure 33 and its legend first, at the same time studying the plate figures to which reference is made in figure 33 b , then to read the portions of the Results in italics consecutively followed by the Discussion, finally studying the detailed Results. Further details of many of the illustrations and tables are available for reference in the Archives of the Royal Society.


The Copley Medal is awarded to Professor B. Katz, F. R. S. Professor Katz’s researches have mainly been concerned with the mechanism of junctional transmission between nerve and muscle, but earlier he played an important part in helping Hodgkin and Huxley to establish the ionic theory of the nervous impulse. He set out to examine the nature of the end-plate potential with intracellular micro-electrodes, and showed that the arrival of a nerve impulse at the motor end-plate had the effect of short-circuiting the resistive membrane of the muscle fibre so as to set up a propagated action potential in the fibre. This led him to the discovery of the spontaneous ‘miniature’ end-plate potentials, which are due to a quanta! random release from the nerve endings of the chemical transmitter acetyl­choline. He went on to develop as a precise and quantitative tool the technique of applying minute quantities of drugs at selected spots by releasing them electro-phoretically from micropipettes, in order to study the pharmacology of the motor end-plate. The concepts and methods introduced by Professor Katz in each phase of this work have been widely applied to study junctional transmission elsewhere, for example in the brain and spinal cord, so that he has had a considerable in­fluence on the development of our ideas about the detailed working of the nervous system.


1971 ◽  
Vol 55 (2) ◽  
pp. 449-468 ◽  
Author(s):  
MARGARET ANDERSON ◽  
I. M. COOKE

1. Glass microelectrodes were used to record intracellular activity from the striated muscle fibres of the heart of the lobster Homarus americanus. 2. In spontaneously beating hearts bursts of impulses are generated at regular intervals by neurones in the cardiac ganglion. These bursts produce depolarizations of the muscle fibres. Each depolarization is associated with a contraction of the heart. The depolarizations consist of many depolarizing steps; each step is related in a one-to-one manner to a nerve impulse and is believed to be an excitatory junction potential (EJP). The depolarizations (400-700 ms duration in different preparations) exhibit a fast rise to a peak (35-40 mV) followed by a plateau (20-25 mV) which decays to the resting level (51.5 ± 3.2 mV, n = 148). 3. Current-voltage curves indicate that the EJPs do not give rise to regenerative membrane responses. 4. Small, spontaneously produced potentials were recorded in the presence of TTX. Autocovariance tests show that the potentials occur independently and are likely to be miniature junction potentials. 5. Polyneuronal innervation of the muscle fibres was demonstrated by applying stimuli of gradually increasing intensity to the distal ends of cut nerves while recording the responses of a muscle fibre. 6. When a train of stimuli is applied at an intensity to evoke activity from a single axon, the first response of a muscle fibre is usually greater than the second; facilitation of the second and subsequent responses takes place. The degree of facilitation developed depends on the frequency of stimulation. Facilitation decays exponentially with a time constant of a few seconds. 7. In two-pulse experiments the second response was depressed when the interpulse intervals were ≤ 0.5 s. 8. Examples of combined facilitation and depression are presented.


1984 ◽  
Vol 221 (1225) ◽  
pp. 375-383 ◽  

Inhibitory junctional currents (i. j. c. s) have been examined in locust muscle fibres to give properties of GABA-channels activated by the neurally released transmitter. A nerve-muscle preparation is described which has proved suitable for voltage-clamp analysis of inhibitory transmission. I. j. c. s were recorded from fibres in which excitatory synapses had been desensitized with glutamate, to abolish excitatory junctional currents. This procedure had no apparent effect on inhibitory channel properties. The time constant of decay of the i. j. c. was 7.7 ± 0.3 ms, slightly exceeding the time constant of the membrane noise induced by externally applied GABA. Peak i. j. c. conductance decreased with hyperpolarization. I. j .c.s showed measurable fluctuations permitting an estimate of the mean size of the quantal events composing the i. j. c. Their mean size coincided with the spontaneously occurring miniature inhibitory junctional currents that could be directly recorded in some fibres. The inhibitory nerve-impulse released an average of 35 transmitter packets at sites distributed along the muscle fibre length. Since each m. i. j. c. produced a current of about 0.6 nA (at V m = — 80 mV, E C1 = — 40 mV) the single quantum of inhibitory transmitter opens 600-1000 postsynaptic chloride channels. This is roughly three to four times the number of channels opened by the excitatory transmitter packet at glutamate synapses in the same fibres.


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