Neuromuscular Depression and the Apparent Depletion of Transmitter in Mammalian Muscle

Thies, Roger

doi:10.1152/jn.1965.28.3.427

Cited by 171 publications

(122 citation statements)

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“…Currents from the selected pyramidal cell are measured with the whole cell recording method, and a small region of the dendritic tree is superfused with one of two solutions that contain the following (in mM): solution 1: NaCl (137), KCl 2), with osmolarity adjusted to 300 mOsm with sucrose. The pipette solution for whole cell recording contained (in mM) potassium gluconate (120), KCI (12), NaCl (5), CaCl2 (1), MaCl2 (2), Hepes (10), EGTA (5), and Na2ATP (2) (pH 7.2).…”

Section: Methodsmentioning

confidence: 99%

Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.

Stevens

Tsujimoto

1995

Proc. Natl. Acad. Sci. U.S.A.

333

267

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Local superfusion of limited dendritic areas with hypertonic or hyperkalemic solutions stimulates the release of quanta from a small population of synapses made on rodent hippocampal neurons maintained in primary culture, and each quantal event can be detected in the postsynaptic neuron. With maintained stimulation, the initial release rate is about 20 quanta per sec per synapse, and this rate declines exponentially to a final low level. These observations can be interpreted as depletion of available quanta and, with this interpretation, a bouton would contain one to two dozen quanta in its readily releasable pool. Tests with a second application of the solution that produces release reveal that the pool of readily releasable quanta is replenished with a time constant of about 10 sec (36°C). The pool of quanta defined in this way may correspond to the population of vesicles docked at the bouton's active zone.Because synapses are so densely packed in brain, the properties of individual, identified boutons are very difficult to investigate. Specifically, no physiological information is available on how many quanta are readily available for release by a single central bouton. Earlier investigators have approached the study of individual central synapses in two ways. First, a giant presynaptic terminal from goldfish bipolar cells has been investigated electrophysiologically with exocytosis and endocytosis detected by measuring changes in membrane capacitance (1, 2). Although this approach has many advantages, a disadvantage is that individual exocytotic events cannot be detected, and the giant terminal contains a large number of specialized release zones that are not typical of most other central synapses. Second, hippocampal synapses have been studied in primary cultures with confocal microscopic techniques that permit rates of exocytosis and endocytosis to be followed optically by the uptake and release of fluorescent dye (3), a method that has been used to address similar issues for the amphibian and mammalian neuromuscular junctions (4,5). This method makes individual boutons available for investigation but has limited temporal and spatial resolution so that single quantal releases cannot be detected.We have exploited the accessibility and low density of synapses made in primary cultures of rodent hippocampal neurons to estimate the number of readily releasable quanta per bouton and the time it takes this pool to be replenished once it is depleted. The method we have employed is to superfuse locally a small, identified population of synapses on a single neuron with a solution that produces exocytosis and to count every miniature excitatory postsynaptic current (mEPSC) that occurs. The high resolution of whole cell recording, together with the relatively low release rates that result when a sufficiently small population of synapses is active, permits us to detect virtually every transmitter quantum released. Two different superfusion solutions ("release solutions") have been employed to produce transmitte...

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Section: Methodsmentioning

confidence: 99%

Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.

Stevens

Tsujimoto

1995

Proc. Natl. Acad. Sci. U.S.A.

333

267

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“…This latter effect is further substantiated by the finding in the present study that aldrin-transdiol enhanced neuromuscular depression. Neuromuscular depression is caused by a gradual decrease of transmitter release per nerve impulse as a result of partial depletion of available transmitter {Otsuka et al Thies, 1965). According to Otsuka and Endo {1960), and Thies (1965) the increase in transmitter release by a drug would always lead to an enhancement of neuromuscular depression if the available transmitter store remained unchanged or decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Neuromuscular depression is caused by a gradual decrease of transmitter release per nerve impulse as a result of partial depletion of available transmitter {Otsuka et al Thies, 1965). According to Otsuka and Endo {1960), and Thies (1965) the increase in transmitter release by a drug would always lead to an enhancement of neuromuscular depression if the available transmitter store remained unchanged or decreased. Thus the enhancement of depression observed in the present experiments might be solely due to the previously augmented transmitter release.…”

Section: Discussionmentioning

confidence: 99%

“…5). This depression is due to a decrease in transmitter release from the nerve terminal Thies, 1965).…”

Section: Neuromuscular Depressionmentioning

confidence: 99%

“…This was done by investigating the effects of aldrin-transdiol on neuromuscular facilitation Miledi, 1968, 1970) and depression Thies, 1965). KC1 2.5, NaH2PO4 0.85, Na2HPO4 2.15 and CaC12 2.0; at pH 7.1--7.3) and after about 5 min, 95% of the bathing solution was changed.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Aldrin-transdiol on neuromuscular facilitation and depression

Akkermans

Bercken

Zalm

1975

European Journal of Pharmacology

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Effects of aldrin-transdiol on neuromuscular facilitation and depression, European J. Pharmacol. 31 (1975) 166--175.The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve--muscle preparations. Conventional techniques of intracellular recordings were used. Aldrin-transdiol caused a marked increase in end-plate potential amplitude under conditions of low quantal content, i.e., in Mg2+-blocked junctions. The increase in end-plate potential amplitude was less pronounced in curarized junctions, in which the transmitter release was not impaired. Concomitant with the increase in end-plate potential size there was a marked enhancement of facilitation during short trains of stimuli applied to the motor nerve. The decay of facilitation was, however, not seriously affected by aldrin-transdiol. These effects may be explained in terms of the known 'calcium hypothesis' by assuming that aldrin-transdiol increases the amount of calcium which enters the nerve terminal during the nerve impulse.The increase in end-plate potential amplitude and in facilitation by aldrin-transdiol was transient. At later stages of poisoning, end-plate potential and facilitation decreased below control level and neuromuscular depression was significantly enhanced. This latter effect may be the result of a direct inhibitory effect of aldrin-transdiol on transmitter mobilization. As far as the fall in end-plate potential amplitude is concerned the known suppressive action of aldrin-transdiol on the chemical sensitivity of the postsynaptic membrane and on the nerve action potential probably plays a part as well. Finally, neuromuscular transmission was completely blocked by aldrintransdiol.

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Local Cooling in Myasthenia

Borenstein¹,

Desmedt²

1975

Arch Neurol

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Weak myasthenic muscles were tested by nerve stimulation both at normal temperature and after local cooling that was accomplished by exposing the skin to ice bags or cold paraffin oil. Reduction of intramuscular temperature from 35 C to 28 C increased the voltage of the bellytendon electrical response, the force of the tetanus elicited by 10/sec or 20/sec nerve stimulation. The myasthenic decrement of successive muscle responses was less marked after cooling, as were "delayed rundown" and "postactivation exhaustion." All these effects were reversed on rewarming the muscle. The abnormal neuromuscular jitter in motor-unit components was also reduced by local cooling. These observations may explain why diagnostic application of repetitive stimulation may be false-negative; muscle temperature must be controlled.

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Neuromuscular Depression and the Apparent Depletion of Transmitter in Mammalian Muscle

Cited by 171 publications

References 0 publications

Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.

Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.

Effects of Aldrin-transdiol on neuromuscular facilitation and depression

Local Cooling in Myasthenia

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