Presynaptic Acetylcholine Receptors Modulate the Time Course of Action Potential-Evoked Acetylcholine Quanta Secretion at Neuromuscular Junctions

Abstract

For effective transmission of excitation in neuromuscular junctions, the postsynaptic response amplitude must exceed a critical level of depolarization to trigger action potential spreading along the muscle-fiber membrane. At the presynaptic level, the end-plate potential amplitude depends not only on the acetylcholine quanta number released from the nerve terminals in response to the nerve impulse but also on a degree of synchronicity of quanta releases. The time course of stimulus-phasic synchronous quanta secretion is modulated by many extra- and intracellular factors. One of the pathways to regulate the neurosecretion kinetics of acetylcholine quanta is an activation of presynaptic autoreceptors. This review discusses the contribution of acetylcholine presynaptic receptors to the control of the kinetics of evoked acetylcholine release from nerve terminals at the neuromuscular junctions. The timing characteristics of neurotransmitter release is nowadays considered an essential factor determining the plasticity and efficacy of synaptic transmission.

Keywords: evoked quantal acetylcholine release; kinetics of the quantal secretion; neuromuscular junction; presynaptic acetylcholine receptors.

Figure 1

Asynchronous evoked phasic ACh release at the frog neuromuscular junction under low extracellular Ca²⁺ concentration and scheme demonstrating the role of asynchronous quantal release after a nerve stimulus in the formation of a multiquantal postsynaptic response. (A) Superimposed extracellular recordings of action potentials of the nerve terminal and uniquantal end-plate potentials under a low extracellular Ca²⁺ concentration. St—nerve stimulus; Aps—nerve action potentials; EPCs—end-plate currents; SD—real synaptic delay. (B) Histogram illustrating the distribution of synaptic delays of the uniquantal EPCs (data from single experiment). The bin size was 0.05 ms. (C) Summation of the uniquantal responses with equal time moments of release (a) and (b) as well as with different time moments of release (c) and (d); dash line and Ecr—the threshold for generation of muscle action potential, i.e., E critical level. (D) Scheme of generation of muscle action potential when the end-plate amplitude reaches the threshold for generation of the muscle action potential. This figure was prepared based on data from [7].

Figure 2

Asynchronous evoked phasic ACh release at extracellular concentration of Ca²⁺ close to the physiological level in the frog neuromuscular junction. (A) Averaged evoked multiquantal EPC recorded intracellularly under a physiological extracellular Ca²⁺ concentration, in the inset—averaged miniature EPC registered in the same neuromuscular junction; (B) the distribution of latent periods obtained by the subtraction from 256 multiquantal EPC curve, the average miniature EPC curve registered at the same neuromuscular junction. The ordinate shows the number of latent periods; the abscissa shows time in msec. This figure was based on [16].

Figure 3

Exogenous ACh desynchronizes the quantal secretion in the frog neuromuscular junction. (A) Superimposed extracellular recordings of action potentials of the nerve terminal and uniquantal end-plate potentials under low extracellular Ca²⁺ concentration in control in the distal part of long nerve terminal; (B) the superposition of uniquantal EPCs in the same synapse after ACh (10 µM) addition in the bathing solution; (C) histogram illustrating the distribution of synaptic delays in control (1) and upon ACh action (2); (D) EPCs recorded in the control conditions (1), in response to 10 µM ACh (2). Reconstructed EPC without taking into account changes in the kinetics of quanta secretion is also shown (3). Note the latter response is larger by 17% than in the curve (2). This figure was based on [34,35,36].