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

Abstract

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.

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

“…The EPC was described in terms of three parameters: amplitude of the EPC, rise time (measured from the time at which the EPC reaches 10% of its amplitude to the time at which it reaches 90%), and time constant of the EPC exponential decay (Zepc). In accordance with physiological data (Del Castillo and Katz 1954;Giniatullin and Khazipov 1991;Giniatullin and al. 1993) the EPC quantal content was chosen to be at least 100 independent identical quanta (MEPC).…”

“…2D, open symbols vs. filled symbols). Thus, the prolongation of EPC rise time up to 1.5 fold in train experiments (Giniatullin and Khazipov 1991;Giniatullin et al 1993) may contribute to only a 6% decrease of the EPC amplitude.…”

“…At the adult vertebrate neuromuscular junction with intact cholinesterase (Giniatullin et al 1993), the duration and amplitude of the multiquantal postsynaptic response is limited by a relatively short mean open time and conductivity of ACh receptor channels (Katz and Miledi 1972;Sakmann and Witzemann, 1989) and by a sufficiently synchronized release of tens (mammals) or even hundreds (amphibia) of quanta from active zones at the nerve terminal (Katz and Miledi 1967;Katz 1969). Any distortion of the optimal pattern of pre-and postsynaptic kinetics might alter the amplitude and time course of synaptic currents (Del Castillo and Katz 1954;Cohen et al 1981 a, b).…”

“…The aim was to determine how Correspondence to: F. Vysko6il changes in the time distribution of quantal release and the time course of a single quantum response (which reflects the mean open time of the ACh receptor channel (Anderson and Stevens 1993;Sakmann and Witzemann 1989)) may affect the resulting EPC. These two factors were chosen and examined together because both of them are variable during natural patterns of synaptic activity (Van der Kloot 1988a; Giniatullin et al 1993) and both of them might be changed by a number of pharmacological agents (e.g. Fu 1994;Van der Kloot 1990).…”

Mechanisms Shaping the Slow Nicotinic Synaptic Current at the Motoneuron-Renshaw Cell Synapse

“…The fast component slowed during a train: 1 (5p) was larger than 1 (1p). This slowing could not be analyzed in detail because the fast decay is superimposed on the rising phase of the slow component, but it resembles the prolongation of the endplate current for a double pulse observed by Magazanik et al (1984) at the neuromuscular junction in conditions of high quantal content, and the slowing of the EPSC observed after increasing the quantal content in both the neuromuscular junction (Giniatullin et al, 1993) and the ciliary ganglion (Stanchev and Sargent, 2011). As discussed by Stanchev and Sargent (2011), these effects are well explained by nonlinear postsynaptic interactions in which ACh released from adjacent sites reaches overlapping areas of the postsynaptic surface (Hartzell et al, 1975).…”