Adrenergic receptors control frequency-dependent switching of the exocytosis mode between “full-collapse” and “kiss-and-run” in murine motor nerve terminal

• Published in: Life sciences (1973) 2022-05, Vol.296, p.120433, Article 120433
• Main Authors: Petrov, Alexey M., Zakirjanova, Guzalia F., Kovyazina, Irina V., Tsentsevitsky, Andrei N., Bukharaeva, Ellya A.
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Acetylcholine release; Adrenergic alpha-2 Receptor Agonists - pharmacology; Adrenergic receptors; Animals; Dexmedetomidine - pharmacology; Diaphragm; Dyes; Endocytosis; Evoked Potentials - drug effects; Exocytosis; Exocytosis - drug effects; Exocytosis - physiology; Fluorescent dyes; Fluorescent Dyes - pharmacokinetics; Fluorescent indicators; Frequency dependence; High frequencies; Kiss-and-run; Membrane fusion; Mice; Mice, Inbred BALB C; Microelectrodes; Nerves; Neuromuscular junction; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Neuromuscular junctions; Neurotransmitter Agents - metabolism; Neurotransmitter release; Neurotransmitters; Noradrenaline; Norepinephrine; Norepinephrine - metabolism; Norepinephrine - pharmacology; Phrenic nerve; Protein turnover; Pyridinium Compounds - pharmacokinetics; Quaternary Ammonium Compounds - pharmacokinetics; Receptors (physiology); Receptors, Adrenergic - metabolism; Receptors, Adrenergic, alpha-2 - metabolism; Respiration; Respiratory system; Stimulation; Stress; Sulforhodamine; Synaptic vesicle exocytosis; Synaptic vesicles; Synaptic Vesicles - metabolism; Unloading; α2-adrenoreceptor
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120433

Neurotransmitter release from the synaptic vesicles can occur through two modes of exocytosis: “full-collapse” or “kiss-and-run”. Here we investigated how increasing the nerve activity and pharmacological stimulation of adrenoceptors can influence the mode of exocytosis in the motor nerve terminal. Recording of endplate potentials with intracellular microelectrodes was used to estimate acetylcholine release. A fluorescent dye FM1–43 and its quenching with sulforhodamine 101 were utilized to visualize synaptic vesicle recycling. An increase in the frequency of stimulation led to a decrease in the rate of FM1–43 unloading despite the higher number of quanta released. High frequency activity promoted neurotransmitter release via the kiss-and-run mechanism. This was confirmed by experiments utilizing (I) FM1–43 dye quencher, that is able to pass into the synaptic vesicle via fusion pore, and (II) loading of FM1–43 by compensatory endocytosis. Noradrenaline and specific α2-adrenoreceptors agonist, dexmedetomidine, controlled the mode of synaptic vesicle recycling at high frequency activity. Their applications favored neurotransmitter release via full-collapse exocytosis rather than the kiss-and-run pathway. At the diaphragm neuromuscular junctions, neuronal commands are translated into contractions necessary for respiration. During stress, an increase in discharge rate of the phrenic nerve shifts the exocytosis from the full-collapse to the kiss-and-run mode. The stress-related molecule, noradrenaline, restricts neurotransmitter release in response to a high frequency activity, and prevents the shift in the mode of exocytosis through α2-adrenoceptor activation. This may be a component of the mechanism that limits overstimulation of the respiratory system during stress. [Display omitted] •Exocytic mode in motor terminal is dependent on frequency of nerve stimulation in diaphragm.•Increased phrenic nerve activity shifts the exocytosis from full-collapse to kiss-and-run.•Noradrenaline and α2-adrenomimetic prevent the shift in the mode of exocytosis.•Noradrenaline restricts neurotransmitter release in response to high frequency activity.•The adrenergic control of exocytosis can limit overstimulation of respiratory system.