Effects of calcium channel blockers on stimulation‐induced changes in transmitter release at the frog neuromuscular junction

Zengel, J E; Lee, David T.; Sosa, María A.; Mosier, Dennis R.

doi:10.1002/syn.890150402

Cited by 11 publications

(7 citation statements)

References 65 publications

(79 reference statements)

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“…Facilitation can also be genuinely increased by a desaturation of the release process. In studies of synapses under conditions of little depression and far from saturation of release, it was shown that reducing Ca 2+ influx decreased facilitation and augmentation phases of enhanced release (78)(79)(80)(81). Elevating external [Ca 2+ ] was often, but not always, able to reverse the effects of Ca 2+ channel blockers.…”

Section: Reducing Ca 2+ Influx Reduces Short-term Enhancementmentioning

confidence: 99%

Short-Term Synaptic Plasticity

Zucker

Regehr

2002

Annu. Rev. Physiol.

4,145

188

3,554

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Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca(2+)]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i. Synaptic depression dominates enhancement at many synapses. Depression is usually attributed to depletion of some pool of readily releasable vesicles, and various forms of the depletion model are discussed. Depression can also arise from feedback activation of presynaptic receptors and from postsynaptic processes such as receptor desensitization. In addition, glial-neuronal interactions can contribute to short-term synaptic plasticity. Finally, we summarize the recent literature on putative molecular players in synaptic plasticity and the effects of genetic manipulations and other modulatory influences.

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Section: Reducing Ca 2+ Influx Reduces Short-term Enhancementmentioning

confidence: 99%

Short-Term Synaptic Plasticity

Zucker

Regehr

2002

Annu. Rev. Physiol.

4,145

188

3,554

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“…At the NMJ, calcium channels also play a key role in the facilitation of transmitter release (Dudel, 1990; Zengel et al ., 1993a, 1993b). Furthermore, a particular arrangement of calcium channel subtypes and the space–time overlapping of calcium microdomains may also contribute to influence this type of short‐term plasticity (Zucker, 1996).…”

Section: Introductionmentioning

confidence: 99%

Differential Ca²⁺‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions

Rosato-Siri

Piriz

Tropper

et al. 2002

Eur J of Neuroscience

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N- and P/Q-type voltage dependent calcium channels (VDCCs) mediate transmitter release at neonatal rat neuromuscular junction (NMJ). Thus the neonatal NMJ allows an examination of the coupling of different subtypes of VDCCs to the release process at a single synapse. We studied calcium dependence of transmitter release mediated by each channel by blocking with omega-conotoxin GVIA the N-type channel or with omega-agatoxin IVA the P/Q-type channel while changing the extracellular calcium concentration ([Ca2+]o). Transmitter release mediated by P/Q-type VDCCs showed steeper calcium dependence than N-type mediated release (average slope 3.6 +/- 0.09 vs. 2.6 +/- 0.03, respectively). Loading the nerve terminals with 10 microm BAPTA-AM in the extracellular solution reduced transmitter release and occluded the blocking effect of omega-conotoxin GVIA (blockade -2 +/- 9%) without affecting the action of omega-agatoxin IVA (blockade 85 +/- 4%). Both VDCC blockers were able to reduce the amount of facilitation produced by double-pulse stimulation. In these conditions facilitation was restored by increasing [Ca2+]o. The facilitation index (fi) was also reduced by loading nerve terminals with 10 microm BAPTA-AM (fi = 1.2 +/- 0.1). The control fi was 2.5 +/- 0.1. These results show that P/Q-type VDCCs were more efficiently coupled to neurotransmitter release than were N-type VDCCs at the neonatal neuromuscular junction. This difference could be accounted for by a differential location of these channels at the release site. In addition, our results indicate that space-time overlapping of calcium domains was required for facilitation.

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“…In support of this, there is now good evidence that Ca 2+ may play more than one role in the secretory process (e.g., Neher and Zucker, 1993). A multisite action of Ca 2+ would explain previously reported differences in the sensitivities of evoked release and stimulation-induced changes in release to Ba 2 and Sr 2+ and to calcium channel blockers (Zengel, Lee, Sosa, and Mosier, 1993;Zengel, Sosa, and Poage, 1993).…”

Section: Discussionmentioning

confidence: 79%

“…Although the mechanisms underlying the various components of increased release are not known, it has long been thought that Ca 2+ may play a critical role in stimulation-induced changes in release (e.g., Katz and Miledi, 1968;Rosenthal, 1969;Miledi and Thies, 1971;Weinreich, 1971;Erulkar and Rahamimoff, 1978). In support of this, we recently reported that blocking Ca ~+ influx into frog motor nerve terminals with Cd 2+ (Zengel, Lee, Sosa, and Mosier, 1993) or the cone snail peptide ~0-conotoxin (Zengel, Sosa, and Poage, 1993) resulted in a reduction of both facilitation and augmentation, suggesting that Ca 2+ entry may be involved in the generation of these two components of increased release.…”

Section: Introductionmentioning

confidence: 86%

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

Zengel¹,

Sosa²,

Poage³

et al. 1994

The Journal of General Physiology

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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. . Journal of General Physiology.80:583-611). It has been suggested that an increased entry of Ca 2+ or an accumulation of intraterminal Ca 2+ may be responsible for one or more of these processes. To test this hypothesis, we have examined the role of intracellular Ca ~+ 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 Ca z+ 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 Ca 2+, 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 Ca 2+ may be acting at more than one site in the nerve terminal.

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Effects of calcium channel blockers on stimulation‐induced changes in transmitter release at the frog neuromuscular junction

Cited by 11 publications

References 65 publications

Short-Term Synaptic Plasticity

Short-Term Synaptic Plasticity

Differential Ca²⁺‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions

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

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Effects of calcium channel blockers on stimulation‐induced changes in transmitter release at the frog neuromuscular junction

Cited by 11 publications

References 65 publications

Short-Term Synaptic Plasticity

Short-Term Synaptic Plasticity

Differential Ca2+‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions

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

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Differential Ca²⁺‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions