Development of desensitization during repetitive end‐plate activity and single end‐plate currents in frog muscle.

Giniatullin, Rashid; Khamitov, G; Khazipov, Roustem; Lg, Magazanik; Nikolsky, E. E.; Snetkov, Vladimir A.; Vyskočil, F.

doi:10.1113/jphysiol.1989.sp017606

Cited by 41 publications

(21 citation statements)

References 18 publications

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“…Proadifen at concentration of 5 ìÒ did not change either the amplitude or the time course (ôMEPC) of the MEPC when present in the muscle bath for 1 h. The initial amplitude and decay time in muscles with intact AChE were 2·7 ± 0·2 nA and 1·1 ± 0·1 ms, respectively; after proadifen application, they were 2·6 ± 0·1 nA and 1·2 ± 0·1 ms, respectively. In agreement with previous findings (Giniatullin et al 1989), the potential dependence of the ôMEPC at membrane potentials between −10 and − 120 mV was also unchanged by proadifen. The similarity of the membrane potential shifts necessary for an e-fold increase in ôMEPC (H coefficient) before (120 ± 8 mV) and 1 h after (110 ± 12 mV) proadifen (n = 5) indicate that this drug did not influence the open time of the AChR ionic channels.…”

Section: Resultssupporting

confidence: 81%

“…In other experiments, the numbers of desensitized AChRs were increased by 5 ìÒ proadifen (SKF 525A) which does not activate the ACh receptor itself but potentiates desensitization, stabilizing the ACh receptors in a nonfunctioning state (Magazanik & Vysko cil, 1973;Sugyiama, Popot & Changeaux, 1976;Magazanik et al 1982;Giniatullin et al 1989Giniatullin et al , 1993b. The effects of proadifen on EPC were also followed in two groups of endplates.…”

Section: Resultsmentioning

confidence: 99%

“…6, Control) (Hartzell et al 1975;Giniatullin et al 1989). In contrast, when endplates were treated first with three 15 min applications of 100 ìÒ ACh interrupted by 20 min intervals of wash-out ( The effect of increased quantal content on the time course of EPCs in one endplate before (þ) and 30 min after treatment with proadifen (±).…”

Section: The Effect Of Cholinesterase Inhibition On Ach and Proadifenmentioning

confidence: 99%

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Desensitization shortens the high‐quantal‐content endplate current time course in frog muscle with intact cholinesterase

Giniatullin¹,

Talantova²,

Vyskočil³

1997

The Journal of Physiology

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1. The relationship between quantal content and prolongation of endplate currents (EPC) was studied in the frog sartorius with intact synaptic acetylcholinesterase. 2. The prolongation of EPC was more pronounced in endplates with a higher quantal content both before and after potentiation of quantal release by 4‐aminopyridine (4‐AP). When the quantal content of EPC was lowered, either by high Mg2+ or repetitive stimulation, the EPC decay constant was reduced. 3. A certain critical value of about 120 quanta per nerve impulse was found, at which point the decay of EPC remained constant even through the quantal content was reduced further. 4. The reduction in both density and number of postsynaptic receptors, produced by alpha‐bungarotoxin and (+)‐tubocurarine led to a profound reduction in EPC decay during the progressive fall in EPC amplitude in both 4‐AP‐treated and ‐untreated endplates. Both drugs are known to produce a shortening of EPC in anti‐cholinesterase (anti‐ChE)‐treated muscles, due to a decrease in receptor density and less frequent repetitive binding of ACh. 5. It is assumed that the prolongation of multiquantal EPC is caused by an increased ACh concentration near the receptors, which may provide the opportunity for repetitive binding even with full cholinesterase activity. The critical quantum content of about 120 might be the number of quanta at which the probability of multiple release at single active zones is increased above zero.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: The Effect Of Cholinesterase Inhibition On Ach and Proadifenmentioning

confidence: 99%

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Desensitization shortens the high‐quantal‐content endplate current time course in frog muscle with intact cholinesterase

Giniatullin¹,

Talantova²,

Vyskočil³

1997

The Journal of Physiology

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“…The right part of the curve is a slow exponential and corresponds to the prolongation of ~mepc by anticholinesterases or by longer channel openings (embryonic receptors with 7subunit (Mishina et al 1968;Sakmann and Witzemann 1989)). The EPC amplitude in this region is affected to a-much smaller extent (Giniatullin et al 1989). When the time dispersion of release is increased, then the EPC amplitude loss is even more pronounced.…”

Section: Resultsmentioning

confidence: 97%

Modelling endplate currents: dependence on quantum secretion probability and decay of miniature current

1995

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Quantification of the time course and amplitude of endplate currents (EPC) was made with respect to dispersion of quanta secretion and to changes in the exponential decay of miniature endplate currents (tau mepc). The relationship between RPC amplitude and tau mepc follows a double-exponential curve with tau1 = 0.3 ms and tau2 = 6 ms. If the amplitude of fully synchronised EPC is taken as 100%, then the loss of EPC amplitude is already 42% with "physiological" parameters of dispersion (the half-rise and decay constant of distribution of secretion probability = 0.5 ms, taumepc = 1 ms). This loss is even more substantial if secretion is more dispersed or miniature endplate currents decay faster.

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“…Desensitization of a muscle cell membrane, i.e., its reduced sensitivity to the neurotransmitter acetylcholine (ACh), may be induced by exogenous cholinomimetics, including depolarizing myorelaxants [10], and by the endogenous ACh released from nerve endings [5,6,12]. How desensitization affects the parameters of synaptic signals and what the functional role of this phenomenon is in skeletal muscle have not been ascertained.…”

Section: Abstract: Synapse; Acetylcholine; Desensitizationmentioning

confidence: 99%

Physiological role of desensitized cholinoceptors in skeletal muscle

Giniatullin

Talantova

1995

Bull Exp Biol Med

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The effect of desensitized cholinoceptors on the time course of end-plate currents was evaluated in frog skeletal muscle at a high (physiological) level of acetylcholine secretion in the presence of active acetylcholinesterase, with two-electrode recording of the membrane potential. When the number of cholinoceptors was small so that they did not appreciably affect the amplitude of end-plate currents or the parameters of onequantum responses (miniature currents), the decay of multiquantum currents was significantly accelerated. Moreover, the presence of cholinoceptors drastically reduced the ability of acetylcholinesterase inhibitors to prolong the decay of end-plate currents. It is suggested that desensitized cholinoceptors in a synapse with a physiological level of acetylcholine secretion and active acetylcholinesterase may bind free acetylcholine with high affinity and thus supplement the well-known physiological role of acetylcholinesterase in limiting the reactivation of postsynaptic membrane cholinoceptors. Key Words: synapse; acetylcholine; desensitizationDesensitization of a muscle cell membrane, i.e., its reduced sensitivity to the neurotransmitter acetylcholine (ACh), may be induced by exogenous cholinomimetics, including depolarizing myorelaxants [10], and by the endogenous ACh released from nerve endings [5,6,12]. How desensitization affects the parameters of synaptic signals and what the functional role of this phenomenon is in skeletal muscle have not been ascertained. Desensitization, if strong, appears to be manifested in lowered amplitudes of synaptie signals as a result of a decrease in the number of receptors capable of opening ion channels when ACh is active. It has also been suggested that desensitized receptors may play a functional role in the redistribution of free ACh in the synaptic cleft through high-affinity binding of the transmitter [13]. Evidence in support of this hypothesis has so far been obtained only for muscles with inhibited acetylcholinesterase and low levels of ACh secretion. In view of this, we tried in this study to elucidate the functional role of desensitized receptors in the presence of active acetylcholinesterase and a high (physiological) level of ACh secretion, i.e., under conditions that, like acetylcholinestemse inhibition, increase the local concentration of this transmitter in the synaptic cleft as compared to its level in the case of one-quantum responses. MATERIALS AND METHODSThe experiment was conducted on neuromuscular preparations of the sciatic nerve-sartorius muscle from Rana ridibunda frogs, with two-electrode recording of the membrane potential. The muscle was continuously peffused with physiological solution of the following composition (mmol/liter): NaC1 113, KC1 2.5, CaC12 1.8, NaHCO 3 2.4; pH 7.2-7.4. To maintain the induced ACh secretion at a high level close to the physiological one, muscle contractions were prevented by transecting the muscle [1]. The nerve was stimulated at a fre-

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Development of desensitization during repetitive end‐plate activity and single end‐plate currents in frog muscle.

Cited by 41 publications

References 18 publications

Desensitization shortens the high‐quantal‐content endplate current time course in frog muscle with intact cholinesterase

Desensitization shortens the high‐quantal‐content endplate current time course in frog muscle with intact cholinesterase

Modelling endplate currents: dependence on quantum secretion probability and decay of miniature current

Physiological role of desensitized cholinoceptors in skeletal muscle

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