scholarly journals A quantitative description of stimulation-induced changes in transmitter release at the frog neuromuscular junction.

1982 ◽  
Vol 80 (4) ◽  
pp. 613-638 ◽  
Author(s):  
K L Magleby ◽  
J E Zengel
Keyword(s):  
Transmitter Release ◽  
Neuromuscular Junctions ◽  
Quantitative Description ◽  
Kinetic Properties ◽  
Frog Neuromuscular Junction ◽  
Endplate Potential ◽  
Multiplicative Type ◽  
Induced Changes ◽  
Endplate Potentials ◽  
Frog Sartorius

Endplate potentials were recorded from frog sartorius neuromuscular junctions under conditions of greatly reduced quantal contents to develop a quantitative description of stimulation-induced changes in transmitter release. Four general models relating potentiation, augmentation, and the first and second components of facilitation to transmitter release were developed. These models were then tested by incorporating equations for the kinetic properties of the four components of increased transmitter release and examining the ability of the resulting sets of equations to predict stimulation-induced changes in transmitter release. Three of the models were essentially consistent with the observation that augmentation had a multiplicative type relationship to facilitation. These models could also predict the effect of frequency and duration of stimulation on endplate potential (EPP) amplitude during and after prolonged (40 s) trains including the response to step changes in stimulation rate. These models extend by about two orders of magnitude the duration of stimulation-induced changes in transmitter release that can be accounted for, and show that the combined kinetic properties of potentiation, augmentation, and the two components of facilitation are generally sufficient to account for these changes.

scholarly journals Differential effects of Ba2+, Sr2+, and Ca2+ on stimulation-induced changes in transmitter release at the frog neuromuscular junction.

1980 ◽  
Vol 76 (2) ◽  
pp. 175-211 ◽  
Author(s):  
J E Zengel ◽  
K L Magleby
Keyword(s):  
Neuromuscular Junction ◽  
Time Constant ◽  
Transmitter Release ◽  
Repetitive Stimulation ◽  
Kinetic Properties ◽  
Bathing Solution ◽  
Frog Neuromuscular Junction ◽  
Induced Changes ◽  
Endplate Potentials ◽  
Frog Sartorius

Endplate potentials (EPP) were recorded from the frog sartorius neuromuscular junction under conditions of low quantal content to study the effect of Ba2+, Sr2+, and Ca2+ on the changes in evoked transmitter release that occur during and after repetitive stimulation. The addition of 0.1-1 mM Ba2+ or Sr2+ to the Ca2+-containing bathing solution, or the replacement of Ca2+ with 0.8-1.4 mM Sr2+, led to a greater increase in EPP amplitudes during and immediately after repetitive stimulation. These changes in release were analyzed in terms of the four apparent components of increased transmitter release that have previously been distinguished on the basis of their kinetic properties. The Ba2+-induced increase in EPP amplitudes was associated with an increase in the magnitude but not the time constant of decay of augmentation. Ba2+ had little effect on potentiation or the first and second components of facilitation. The Sr2+-induced increase in EPP amplitudes was associated with an increase in the magnitude and the time constant of decay of the second component of facilitation. Sr2+ had little effect on potentiation, augmentation, or the first component of facilitation. The selective effects of Ba2+ on augmentation and of Sr2+ on the second component of facilitation were reversible and could be obtained in the presence of the other ion. The addition of 0.1-0.3 mM Ca2+ to the bathing solution had little effect on potentiation, augmentation, or the two components of facilitation. These results provide pharmacological support for the proposal that there are four different components of increased transmitter release associated with repetitive stimulation and suggest that the underlying factors in the nerve terminal that give rise to these components can act somewhat independently of one another.

scholarly journals Changes in miniature endplate potential frequency during repetitive nerve stimulation in the presence of Ca2+, Ba2+, and Sr2+ at the frog neuromuscular junction.

1981 ◽  
Vol 77 (5) ◽  
pp. 503-529 ◽  
Author(s):  
J E Zengel ◽  
K L Magleby
Keyword(s):  
Nerve Stimulation ◽  
Transmitter Release ◽  
Neuromuscular Junctions ◽  
Fourth Power ◽  
Bathing Solution ◽  
Frog Neuromuscular Junction ◽  
Repetitive Nerve Stimulation ◽  
Time Constants ◽  
Endplate Potential ◽  
Induced Changes

Miniature endplate potentials (MEPPs) were recorded from frog sartorious neuromuscular junctions under conditions of reduced quantal contents to study the effect of repetitive nerve stimulation on asynchronous (tonic) quantal transmitter release. MEPP frequency increased during repetitive stimulation and then decayed back to the control level after the conditioning trains. The decay of the increased MEPP frequency after 100-to 200-impulse conditioning trains can be described by four components that decayed exponentially with time constants of about 50 ms, 500 ms, 7 s, and 80 s. These time constants are similar to those for the decay of stimulation-induced changes in synchronous (phasic) transmitter release, as measured by endplate potential (EPP) amplitudes, corresponding, respectively, to the first and second components of facilitation, augmentation, and potentiation. The addition of small amounts of Ca2+ or Ba2+ to the Ca2+-containing bathing solution, or the replacement of Ca2+ with Sr2+, led to a greater increase in the stimulation-induced increases in MEPP frequency. The Sr-induced increase in MEPP frequency was associated with an increase in the second component of facilitation of MEPP frequency; the Ba-induced increase with an increase in augmentation. These effects of Sr2+ and Ba2+ on stimulation-induced changes in MEPP frequency are similar to the effects of these ions on stimulation-induced changes in EPP amplitude. These ionic similarities and the similar kinetics of decay suggest that stimulation induced changes in MEPP frequency and EPP amplitude have some similar underlying mechanisms. Calculations are presented which show that a fourth power residual calcium model for stimulation-induced changes in transmitter release cannot readily account for the observation that stimulation-induced changes in MEPP frequency and EPP amplitude have similar time-courses.

scholarly journals Augmentation and facilitation of transmitter release. A quantitative description at the frog neuromuscular junction.

1982 ◽  
Vol 80 (4) ◽  
pp. 583-611 ◽  
Author(s):  
J E Zengel ◽  
K L Magleby
Keyword(s):  
Transmitter Release ◽  
Neuromuscular Junctions ◽  
Quantitative Description ◽  
Nerve Impulse ◽  
Power Relationship ◽  
Frog Neuromuscular Junction ◽  
First Order ◽  
First Order Kinetics ◽  
Frequency Of Stimulation ◽  
Endplate Potentials

Endplate potentials were recorded from frog and toad sartorius neuromuscular junctions under conditions of greatly reduced quantal contents. The magnitudes of augmentation increased with the duration and frequency of stimulation, often increasing at an accelerating rate during 10-20-s conditioning trains. The magnitudes of the first and second components of facilitation also increased, but reached apparent steady state values within the first few seconds of stimulation. These observations could be accounted for by assuming (a) that augmentation and the first and second components of facilitation arise from underlying factors in the nerve terminal that act to increase transmitter release; (b) that each nerve impulse adds an increment to each of the underlying factors; (c) that the magnitude of the increment typically increases during the train for augmentation but remains constant for the components of facilitation; and (d) that the underlying factors decay with first-order kinetics with time constants of approximately 7 s for augmentation and 60 and 500 ms for the first and second components of facilitation, respectively. The increments of facilitation added by each impulse were about twice as large in the toad as in the frog. Facilitation was described better by assuming a power relationship between the underlying factor and the observed facilitation than by assuming a linear relationship. Augmentation was described by assuming either a linear or power relationship.

scholarly journals Regeneration of the active zone at the frog neuromuscular junction.

1984 ◽  
Vol 98 (5) ◽  
pp. 1685-1695 ◽  
Author(s):  
C P Ko
Keyword(s):  
Active Zone ◽  
Transmitter Release ◽  
Neuromuscular Junctions ◽  
Freeze Fracture ◽  
Frog Neuromuscular Junction ◽  
Normal Pattern ◽  
Intramembrane Particles ◽  
Total Length ◽  
Secondary Stage ◽  
Active Zones

The active zone is a unique specialization of the presynaptic membrane and is believed to be the site of transmitter release. The formation of the active zone and the relationship of this process to transmitter release were studied at reinnervated neuromuscular junctions in the frog. At different times after a nerve crush, the cutaneous pectoris muscles were examined with intracellular recording recording and freeze-fracture electron microscopy. The P face of a normal active zone typically consists of two double rows of particles lined up in a continuous segment located opposite a junctional fold. In the initial stage of reinnervation, clusters of large intramembrane particles surrounding membrane elevations appeared on the P face of nerve terminals. Like normal active zones, these clusters were aligned with junctional folds. Vesicle openings, which indicate transmitter release, were seen at these primitive active zones, even though intramembrane particles were not yet organized into the normal pattern of two double rows. The length of active zones at this stage was only approximately 15% of normal. During the secondary stage, every junction was reinnervated and most active zones had begun to organize into the normal pattern with normal orientation. Unlike normal, there were often two or more discontinuous short segments of active zone aligned with the same junctional fold. The total length of active zone per junctional fold increased to one-third of normal, mainly because of the greater number of segments. In the third stage, the number of active zone segments per junctional fold showed almost no change when compared with the secondary stage. However, individual segments elongated and increased the total length of all active zone segments per junctional fold to about two-thirds of the normal length. The dynamic process culminated in the final stage, during which elongating active zones appeared to join together and the number of active zone segments per junctional fold decreased to normal. Thus, in most regions, regeneration of the active zones was complete. These results suggest that the normal organization of two double rows is not necessary for the active zone to be functional. Furthermore, localization of regenerating active zones is related to junctional folds and/or their associated structures.

Effects of adenosine on Ca2+ entry in the nerve terminal of the frog neuromuscular junction

1999 ◽  
Vol 77 (9) ◽  
pp. 707-714 ◽  
Author(s):  
Richard Robitaille ◽  
Sébastien Thomas ◽  
Milton P Charlton
Keyword(s):  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Nerve Stimulation ◽  
High Frequency ◽  
Transmitter Release ◽  
Synaptic Depression ◽  
Presynaptic Terminal ◽  
Nerve Terminals ◽  
Frog Neuromuscular Junction ◽  
Induced Changes

This study aimed to test whether nerve-evoked and adenosine-induced synaptic depression are due to reduction in Ca2+ entry in nerve terminals of the frog neuromuscular junction. Nerve terminals were loaded with the fluorescent Ca2+ indicator fluo 3 (fluo 3-AM) or loaded with dextran-coupled Ca2+ green-1 transported from the cut end of the nerve. Adenosine (10-50 µM) did not change the resting level of Ca2+ in the presynaptic terminal, whereas it induced large Ca2+ responses in perisynaptic Schwann cells, indicating that adenosine was active and might have induced changes in the level of Ca2+ in the nerve terminal. Ca2+ responses in nerve terminals could be induced by nerve stimulation (0.5 or 100 Hz for 100 ms) over several hours. In the presence of adenosine (10 µM), the size and duration of the nerve-evoked Ca2+ responses were unchanged. When extracellular Ca2+ concentration was lowered to produce the same reduction in transmitter release as the application of adenosine, Ca2+ responses induced by nerve stimulations were reduced by 40%. This indicates that changes in Ca2+ responsible for the decrease in release should have been detected if the mechanism of adenosine depression involved partial block of Ca2+ influx. Ca2+ responses evoked by prolonged high frequency trains of stimuli (50 Hz for 10 or 30 s), which caused profound depression of transmitter release, were sustained during the whole duration of the stimulation, and adenosine had no effect on these responses. These data indicate that neither adenosine induced synaptic depression nor stimulation-induced synaptic depression are caused by reductions in Ca2+ entry into the presynaptic terminal in the frog neuromuscular junction.Key words: adenosine, Ca2+, nerve terminal, transmitter release, synaptic depression.

Oscillation period of MEPP frequency at frog neuromuscular junctions is inversely correlated with release efficacy and independent of acute Ca 2+ loading

1989 ◽  
Vol 237 (1289) ◽  
pp. 489-499 ◽  
Keyword(s):  
Neuromuscular Junctions ◽  
Oscillation Period ◽  
Ringer Solution ◽  
Time Interval ◽  
Frog Neuromuscular Junction ◽  
Periodic Oscillations ◽  
Endplate Potential ◽  
Intracellular Ca ◽  
Miniature Endplate Potential ◽  
Post Tetanic Potentiation

Periodic oscillations in miniature endplate potential (MEPP) frequency have been described at the frog neuromuscular junction. It is assumed that the periodic oscillations in MEPP frequency reflect cytosolic oscillations in intracellular Ca 2+ concentration. In the course of a study related to describing the differences between weak and strong neuro­muscular junctions by using the post-tetanic potentiation of MEPP fre­quency, we noted periodic oscillations in MEPP frequency in the first few minutes after a tetanus. The period of this oscillation (i. e. the time interval of one complete oscillation cycle) was inversely related to syn­aptic release efficacy, as measured by quantal content released per 100 μ m of nerve terminal length. Junctions of high release efficacy have an oscillation period of 20 s or less whereas the oscillations in weaker junc­tions have periods of up to 60 s or longer. This relation is very similar during post-tetanic recovery in either a calcium containing Ringer solution or in a zero calcium-EGTA Ringer solution, indicating that external calcium is not necessary to express the phenomenon. We also found that the oscillations are apparent in resting junctions preceding a tetanus and that they are similar in period and show the same inverse relation to synaptic strength.

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