The Role of Presynaptic Ryanodine Receptors in Regulation of the Kinetics of the Acetylcholine Quantal Release in the Mouse Neuromuscular Junction

To determine the role of presynaptic ryanodine receptors in the regulation of the kinetics of neurotransmitter quantum secretion caused by a nerve impulse in the experiments on the mouse neuromuscular junction, temporal parameters of phase synchronous and asynchronous delayed release of acetylcholine under the conditions of ryanodine receptors block and rhythmic stimulation were examined. The analysis of histograms of synaptic delays of the uni-quantal end-plate currents registered within 50 ms after the onset of the presynaptic action potential showed that ryanodine receptor blockers ryanodine, TMB-8, and dantrolene reduced the intensity of both phase synchronous and delayed asynchronous release of the mediator. The proportion of quanta released synchronously increased at the expense of reduction of quantum number forming the delayed asynchronous release, i.e., there was a redistribution of quanta between synchronous and asynchronous phases of secretion. Block of ryanodine receptors also reduced the fluorescence intensity of a specific fluorescent calcium-sensitive dye Fluo-3 AM, which indicates a decrease in the intracellular calcium ion concentration. Thus, the presynaptic ryanodine receptors control the intracellular content of calcium ions under repetitive stimulation of the nerve endings and contribute to the modulation of the time parameters of the evoked release of the neurotransmitter quanta by increasing the intensity of the delayed asynchronous release of neurotransmitter.