scholarly journals Role of intracellular Ca2+ in stimulation-induced increases in transmitter release at the frog neuromuscular junction.

1994 ◽  
Vol 104 (2) ◽  
pp. 337-355 ◽  
Author(s):  
J E Zengel ◽  
M A Sosa ◽  
R E Poage ◽  
D R Mosier
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Cyclopiazonic Acid ◽  
Progressive Increase ◽  
Repetitive Stimulation ◽  
Frog Neuromuscular Junction ◽  
Quantal Content ◽  
Carbonyl Cyanide ◽  
Stimulation Of

Under conditions of reduced quantal content, repetitive stimulation of a presynaptic nerve can result in a progressive increase in the amount of transmitter released by that nerve in response to stimulation. At the frog neuromuscular junction, this increase in release has been attributed to four different processes: first and second components of facilitation, augmentation, and potentiation (e.g., Zengel, J. E., and K. L. Magleby. 1982. Journal of General Physiology. 80:583-611). It has been suggested that an increased entry of Ca2+ or an accumulation of intraterminal Ca2+ may be responsible for one or more of these processes. To test this hypothesis, we have examined the role of intracellular Ca2+ in mediating changes in end-plate potential (EPP) amplitude during and after repetitive stimulation at the frog neuromuscular junction. We found that increasing the extracellular Ca2+ concentration or exposing the preparation to carbonyl cyanide m-chlorophenylhydrazone, ionomycin, or cyclopiazonic acid all led to a greater increase in EPP amplitude during conditioning trains of 10-200 impulses applied at a frequency of 20 impulses/s. These experimental manipulations, all of which have been shown to increase intracellular levels of Ca2+, appeared to act by increasing primarily the augmentation component of increased release. The results of this study are consistent with previous suggestions that the different components of increased release represent different mechanisms, and that Ca2+ may be acting at more than one site in the nerve terminal.

Differences in presynaptic action of 4-aminopyridine and tetraethylammonium at frog neuromuscular junction

1987 ◽  
Vol 65 (5) ◽  
pp. 747-752 ◽  
Author(s):  
M. I. Glavinović
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Action Potentials ◽  
Time Course ◽  
Potassium Conductance ◽  
Frog Neuromuscular Junction ◽  
Quantal Content ◽  
Low Concentrations ◽  
Voltage Dependent ◽  
Intracellular Ca

4-Aminopyridine markedly potentiates transmitter release at the frog cutaneous pectoris neuromuscular junction by increasing the quantal content even when applied at low concentrations (5–20 μM). This enhancement of transmitter release is associated with greater minimum synaptic latency, but the dispersion of the synaptic latencies does not appear much affected. This is in contrast with the action of tetraethylammonium (0.2–0.5 mM) in which case similar enhancement of transmitter release results not only in larger minimum synaptic latency but also in greater dispersion of the synaptic latencies. The time course of transmitter release associated with enhanced transmitter output is hence much more prolonged in the presence of tetraethylammonium than 4-aminopyridine, at least for low concentrations of 4-aminopyridine (5–20 μM). This indicates that their presynaptic actions differ significantly. This conclusion is further strengthened by the finding that unlike tetraethylammonium, 4-aminopyridine induces bursts of release, presumably by producing multiple action potentials in the nerve terminal. Tetraethylammonium probably acts by blocking the delayed potassium conductance, but the blockade of Ca2+-activated K+ conductance cannot be excluded. 4-Aminopyridine, however, probably blocks the fast inactivating (IA) K+ current, but it also may be acting directly on the voltage-dependent Ca2+ conductance or on the intracellular Ca2+ buffering.

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.

Dynamics of Excitatory Transmitter Release: Analysis of Synaptic Responses in CA3 Hippocampal Neurons After Repetitive Stimulation of Afferent Fibers

1998 ◽  
Vol 79 (4) ◽  
pp. 1977-1988 ◽  
Author(s):  
Marco Canepari ◽  
Enrico Cherubini
Keyword(s):  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Repetitive Stimulation ◽  
Patch Clamp Technique ◽  
Afferent Fibers ◽  
Presynaptic Mechanisms ◽  
Release Analysis ◽  
Excitatory Transmitter ◽  
Stimulation Of ◽  
Synaptic Responses

Canepari, Marco and Enrico Cherubini. Dynamics of excitatory transmitter release: analysis of synaptic responses in CA3 hippocampal neurons after repetitive stimulation of afferent fibers. J. Neurophysiol. 79: 1977–1988, 1998. The patch-clamp technique (whole cell configuration) was used to record excitatory postsynaptic currents (EPSCs) evoked by repetitive stimulation (4 pulses at 50-ms intervals) of afferent fibers in the stratum lucidum-radiatum. Different synaptic behaviors (EPSC patterns) were classified in terms of facilitation or depression of the mean amplitude of the second, third, and fourth EPSC with respect to the previous one. A large variety of EPSC patterns was observed by stimulating different afferent fibers. Experiments with the mGluR2/mGluR3 agonist 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (1 μM), a compound that reduces release at mossy but not at associative commissural fibers and therefore allows to identify the origin of synaptic responses, showed that particular EPSC patterns could not be associated to the activation of a specific type of synaptic input. To investigate the role of the probability of release in the dynamics of synaptic activity, the extracellular calcium concentration was varied from 0.8 to 4 mM in several experiments. EPSC patterns dominated by depression, characteristics of high release probability conditions, could be observed in the majority of the cases in the presence of higher calcium concentrations. A quantitative model for dynamics of transmitter release has been developed. Experimental results were compared with data computed with the model taking into account the probability of release and the time course of reavailability. This work indicates that short-term changes of presynaptic conditions occurring during a train of action potentials can account for the high variability of EPSC responses. The model that is proposed also suggests a general method of experimental data analysis to investigate the possible presynaptic mechanisms underlying long-lasting changes in synaptic efficacy.

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