Giant miniature end‐plate potentials at the untreated and emetine‐treated frog neuromuscular junction.

Alkadhi, Karim A.

doi:10.1113/jphysiol.1989.sp017627

Cited by 15 publications

(8 citation statements)

References 36 publications

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“…At rat neuromuscular junction more giants appeared at 35 'C (5-8 %) than at 16 'C (0-61 %) (Heinonen, Jansson & Tolppanen, 1982). Acid Tyrode solution inhibited both the quantal size increase by hypertonic treatment and the higher frequency of giants produced by emetine (Alkadhi, 1989). Third, both the large miniatures and the giant MEPPs (Lupa, Tabti, Thesleff, Vyskocil & Yu, 1986) are reduced in size a few minutes after exposure to vesamicol.…”

Section: Large Quanta and Giant Miniaturesmentioning

confidence: 91%

Increasing quantal size at the mouse neuromuscular junction and the role of choline.

Kloot

1991

The Journal of Physiology

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SUMMARY1. In frog a variety of treatments have been shown to increase quantal size at the neuromuscular junction (NMJ), apparently by releasing more acetylcholine (ACh) per quantum. The present experiments were undertaken to see whether similar changes occur at the mouse NMJ.2. None of the hormones tested, adrenaline, insulin or corticosteroids, significantly increased quantal size at the mouse NMJ.3. Soaking diaphragms in hypertonic solution (about 475 mosmol/kg) for 15-30 min roughly doubled the size of miniature endplate potentials (MEPPs), miniature endplate currents (MEPCs), and uniquantal endplate potentials (EPPs). We will refer to these as 'large quanta'. Note that all of the measurements were made after returning the preparation to normal (Tyrode) solution.4. In frog hypertonic solution made with sodium gluconate replacing NaCl increases quantal size four-rather than two-fold. In mouse there was little difference in the effects of solutions made with the two anions. In Cl--free hypertonic solution, made with sodium gluconate and SO42-solutions, quantal size increase is somewhat less, so there may be a role for Cl-in enlarging quantal size.5. After hypertonic treatment, quantal size remained elevated for at least 1 h and then gradually declined back to usual levels. The data suggest a gradual decrease in mean quantal size, rather than the appearance of a new subpopulation of smaller quanta.6. Hypertonic treatment did not change the endplate depolarization in response to ionophoretically applied ACh. This suggests that the increased quantal size is not due to a postsynaptic change. Large MEPP's disappear in the presence of tubocurarine and reappear when the drug is washed away.7. Vesamicol is an inhibitor of active ACh uptake into isolated synaptic vesicles.5 #m-vesamicol has no detectable postjunctional effect. However, when vesamicol was included in the Tyrode and the hypertonic solutions the increase in quantal size was blocked. This is further evidence that the large quanta are produced by the release of more ACh per quantum. 8. Even when added after the hypertonic treatment, vesamicol soon decreased quantal size back to the normal level. Two other inhibitors of active ACh uptake into vesicles, tetraphenylboron (TPB) and hexanitrodiphenylamine (HNPA) also de-MS 8417 S. P. YU AND W. VAN DER KLOOT creased quantal size after hypertonic treatment, apparently by a presynaptic action. This suggests that the additional ACh that produces large miniatures may be incorporated into the quanta shortly before release.9. Experiments were undertaken to test the hypothesis that the additional ACh added to the quanta is newly synthesized transmitter, produced by the acetylation of choline brought into the terminal by the high-affinity choline transport system (HAChT). The formation of large quanta was blocked when the solutions contained hemicholinium-3 (HC-3), an inhibitor of HAChT. At the concentrations used, HC-3 had no notable effect on the postjunctional acetylcholine receptor (AChR). After quantal size was incre...

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Section: Large Quanta and Giant Miniaturesmentioning

confidence: 91%

Increasing quantal size at the mouse neuromuscular junction and the role of choline.

Kloot

1991

The Journal of Physiology

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“…However, similar rhythmic discharge in isolated ganglia is also seen on treatment with emetine, a protein synthesis inhibitor not known to be a K + channel blocker (18,19). Interestingly, both 4AP and emetine have been shown to induce Ca 2+ -independent giant miniature endplate potentials at the neuromuscular junction (19)(20)(21)(22). In this report, we characterized a highly rhythmic discharge induced by low temperature or drugs in isolated mammalian sympathetic ganglia.…”

mentioning

confidence: 55%

“…More recent work reported a significant increase in the abdominal afferent vagus nerve activity after treatment with emetine (39). Although the action of emetine is variable from tissue to tissue, these findings suggest that the drug generally increases transmitter secretion at the synaptic regions (19,21,22). The rhythmic discharge probably results from a decrease in K + efflux, which leads to a gradual depolarization and firing when the threshold is reached.…”

Section: Discussionmentioning

confidence: 86%

“…Although emetine induced Ca 2+ -independent spontaneous release at the frog neuromuscular junction (19,22), its action in ganglia was dependent on the presence of Ca 2+ (see Figure 7). The removal of Ca 2+ from the bathing Locke solution resulted in the disappearance of the rhythmic discharge, which promptly returned when Ca 2+ was reintroduced (see Figure 7).…”

Section: Emetinementioning

confidence: 96%

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Rhythmic Discharge Induced by Temperature Variation and Drugs in Isolated Sympathetic Ganglia

Alkadhi

2008

Clinical and Experimental Hypertension

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Isolated sympathetic ganglia from various mammalian species fire spontaneous, rhythmic discharge when exposed to low temperatures. Extracellular recording from rat, guinea pig, and rabbit superior cervical ganglia as well as dog lumbar ganglion revealed large single potentials or bursts of potentials, occurring at regular intervals, when the bath temperature was kept between 15-30 degrees C. When the temperature was reduced below 15 degrees C or raised above 30 degrees C, the rhythmic discharge decreased in frequency and finally stopped. Rhythmic discharge also appeared when ganglia were treated with emetine or the K(+) channel blockers, cesium and 4-aminopyridine. The frequency and amplitude of potentials and the pattern of rhythm varied from ganglion to ganglion. The single potential or rhythmic burst firing seemed to originate from a single unit or multiple discharging units, as indicated by the amplitude and frequency of the potentials in a burst. The discharge was abolished by ganglionic blocking agents or by the absence of Ca(2+), suggesting a presynaptic origin. The spontaneous rhythmic discharge may be important as a support mechanism for the cardiovascular system in victims of exposure to extreme cold temperature.

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“…Alternative hypotheses, suggest that larger MEPPs represent the whole release of transmitter from a single vesicle, while sub-quanta occur as a result of short spurts of transmitter. The release of spontaneous transmitter resulting in larger than normal MEPPs has previously been observed in multiple models, including the SOD1 G93A model of ALS (Liley, 1957;Alkadhi, 1989;Sellin et al, 1996;Rocha et al, 2013). These 'giant' MEPPs are caused by the single release of a large volume of ACh, which saturates AChRs at the postsynaptic membrane.…”

Section: Altered Spontaneous Release Properties Suggest Presynaptic Amentioning

confidence: 87%

The functional role of laminins-α4 and -β2 in development of the neuromuscular junction

Chand¹

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The precise development and organisation of the neuromuscular junction (NMJ) is critical for the production of efficient neurotransmission signals. Disruption of these specialisations may result in severely altered transmission properties at the NMJ.Signalling and adhesion molecules have long been established to be key mediators in the distribution of synaptic specialisations. The basal lamina acts to maintain stability of the associated tissue and contains a number of these signalling and adhesion molecules. The laminins, a family of large multimeric proteins, are one of the key components of the basal lamina that act as specific cell regulators and provide mechanical stability. Laminins have been shown to form an interconnecting network that assists in stabilisation of the basal lamina and provides attachment sites for other basal lamina components. The synapse specific laminin chains, -α4, -α5, and -β2, play an essential role in differentiation and organisation of the NMJ. These chains form the laminin isoforms, laminin-221 (α2β2γ1), laminin-421 (α4β2γ1), and laminin-521 (α5β2γ1).Laminin-β2, found in each of the three synapse specific isoforms, has been shown to organise presynaptic specialisations at the developing NMJ. In vitro laminin-β2 is able to interact directly with N-type and P/Q-type voltage-gated calcium This study examined the role of laminin-β2 in the organisation of N-and P/Q-type VGCCs at active zones of developing postnatal day 8 (P8) and matured, postnatal day 18 (P18) NMJs.The contribution of each channel to the release of transmitter was assessed using intracellular electrode recordings of end-plate potentials (EPPs). The VGCC toxins, ω-conotoxin-GVIA and ω-agatoxin-IVA, were used to specifically target N-and P/Q-type NMJs displayed significantly higher levels of synaptic depression under high frequency stimuli and altered paired pulse facilitation compared to wild-type littermates. Analysis of the binomial parameters of neurotransmitter release demonstrated a decrease in quantal release as a result of a decrease in the number of active release sites, but not in the average probability of transmitter release from these sites. Our functional findings suggest alterations in the short-term plasticity of the NMJ and possibly defective recycling of ii synaptic vesicles and/or the calcium handling at lama4 -/-NMJs. We propose that alterations to synapsin I and its associated molecules may be partly responsible for the changes in neurotransmission observed at lama4 -/-NMJs. Our findings demonstrate altered distribution and expression of presynaptic components associated with active zones, specifically an increase in the number of synaptic vesicles and a decrease in the density of the fluorescently labelled Bassoon at the active zone region. Our results suggest that the fewer active release sites may compensate for the deficits of the lama4 -/-NMJs by alterations to pre-and postsynaptic specialisations.In conclusion, this thesis has identified that laminins-α4 and -β2 play fundamental role...

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Giant miniature end‐plate potentials at the untreated and emetine‐treated frog neuromuscular junction.

Cited by 15 publications

References 36 publications

Increasing quantal size at the mouse neuromuscular junction and the role of choline.

Increasing quantal size at the mouse neuromuscular junction and the role of choline.

Rhythmic Discharge Induced by Temperature Variation and Drugs in Isolated Sympathetic Ganglia

The functional role of laminins-α4 and -β2 in development of the neuromuscular junction

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