Abstract
The long history of studies on the effect of catecholamines on synaptic transmission does not answer the main question about the mechanism of their action on quantal release in the neuromuscular junction. Currently, interest in catecholamines has increased not only because of their widespread use in the clinic for the treatment of cardiovascular and pulmonary diseases but also because of recent data on their possible use for the treatment of certain neurodegenerative diseases, muscle weakness and amyotrophic sclerosis. Nevertheless, the effects and mechanisms of catecholamines on acetylcholine release remain unclear. We investigated the action of noradrenaline and adrenaline on the spontaneous and evoked quantal secretion of acetylcholine in the neuromuscular junction of the rat soleus muscle. Noradrenaline (10 μM) did not change the spontaneous acetylcholine quantal release, the number of released quanta after nerve stimulation, or the timing of the quantal secretion. However, adrenaline at the same concentration increased spontaneous secretion by 40%, increased evoked acetylcholine quantal release by 62%, and synchronized secretion. These effects differ from those previously described by us in the synapses of the frog cutaneous pectoris muscle and mouse diaphragm. This indicates specificity in catecholamine action that depends on the functional type of muscle and the need to take the targeted type of muscle into account in clinical practice.
This is a preview of subscription content, log in via an institution to check access.
References
Abdullahi A, Wang V, Auger C, Patsouris D, Amini-Nik S, Jeschke MG (2019) Catecholamines induce endoplasmic reticulum stress via both alpha and beta receptors. Shock. https://doi.org/10.1097/SHK.0000000000001394
Anderson AJ, Harvey AL (1988) Effects of the facilitatory compounds catechol, guanidine, noradrenaline and phencyclidine on presynaptic currents of mouse motor nerve terminals. Arch Pharmacol 338:133–137
Barret EE, Stevens CF (1972) The kinetics of transmitter release at the frog neuromuscular junction. J Physiol 227:691–708
Bartus RT, Bétourné A, Basile A, Peterson BL, Glass J, Boulis NM (2016) β2-Adrenoceptor agonists as novel, safe and potentially effective therapies for amyotrophic lateral sclerosis (ALS). Neurobiol Dis 85:11–24. https://doi.org/10.1016/j.nbd.2015.10.006
Bowman WC, Raper C (1962) Adrenaline and slow-contracting skeletal muscles. Nature 6(193):41–43
Bowman WC, Raper C (1967) Adrenotropic receptors in skeletal muscle. Ann N Y Acad Sci 139(3):741–753. https://doi.org/10.1111/j.1749-6632.1967.tb41241.x
Bukcharaeva EA, Kim KC, Moravec J, Nikolsky EE, Vyskocil F (1999) Noradrenaline synchronizes evoked quantal release at frog neuromuscular junctions. J Physiol 517:879–888. https://doi.org/10.1111/j.1469-7793.1999.0879s.x
Bukharaeva E, Nikolskii E (2012) Changes in the kinetics of evoked secretion of transmitter quanta—an effective mechanism modulating the synaptic transmission of excitation. Neurosci Behav Physiol 42:153–160
Bukharaeva EA, Samigullin D, Nikolsky EE, Magazanik LG (2007) Modulation of the kinetics of evoked quantal release at mouse neuromuscular junctions by calcium and strontium. J Neurochem 100:939–949. https://doi.org/10.1111/j.1471-4159.2006.04282.x
Burke G, Hiscock A, Klein A, Niks EH, Main M, Manzur AY, Ng J, De-Vile C et al (2013) Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscul Disord 23:170–175. https://doi.org/10.1016/j.nmd.2012.11.004
Bylund DB (2007) Alpha- and beta-adrenergic receptors: Ahlquist's landmark hypothesis of a single mediator with two receptors. Am J Physiol Endocrinol Metab 293(6):1479–1481. https://doi.org/10.1152/ajpendo.00664.2007
Cairns S, Borrani F (2015) β-Adrenergic modulation of skeletal muscle contraction: key role of excitation—contraction coupling. J Physiol 593:4713–4727. https://doi.org/10.1113/JP270909
Cairns SP, Dulhunty AF (1993) The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat. Br J Pharmacol 110(3):1133–1141. https://doi.org/10.1111/j.1476-5381.1993.tb13932.x
Decorte N, Lamalle L, Carlier PG, Giacomini E, Guinot M, Levy P, Verges S, Wuyam B (2015) Impact of salbutamol on muscle metabolism assessed by 31P NMR spectroscopy. Scand J Med Sci Sports 25:e267–e273. https://doi.org/10.1111/sms.12312
Engel AG, Shen XM, Selcen D, Sine SM (2015) Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol 14:420–434. https://doi.org/10.1016/S1474-4422(14)70201-7
Ghazanfari N, Morsch M, Tse N, Reddel SW, Phillips WD (2014) Effects of the ß2-adrenoceptor agonist, albuterol, in a mouse model of anti-MuSK Myasthenia Gravis. PLoS ONE 9(2):e87840. https://doi.org/10.1371/journal.pone.0087840
Ginsborg BL, Hirst GD (1971) Prostaglandin E1 and noradrenaline at the neuromuscular junction. Br J Pharmacol 42(1):153–154
Huang CH, Moser T (2018) Ca2+ regulates the kinetics of synaptic vesicle fusion at the afferent inner hair cell synapse. Front Cell Neurosci 12:364. https://doi.org/10.3389/fncel.2018.00364
Joassard OR, Durieux AC, Freyssenet DG (2013) β2-Adrenergic agonists and the treatment of skeletal muscle wasting disorders. Int J Biochem Cell Biol 45(10):2309–2321. https://doi.org/10.1016/j.biocel.2013.06.025
Juel C (1988) The effect of β2-adrenoceptor activation on ion-shifts and fatigue in mouse soleus muscles stimulated in vitro. Acta Physiol Scand 134:209–216. https://doi.org/10.1111/j.1748-1716.1988.tb08481.x
Kaeser PS, Regehr WG (2014) Molecular mechanisms for synchronous, asynchronous, and spontaneous neurotransmitter release. Annu Rev Physiol 76:333–363. https://doi.org/10.1146/annurev-physiol-021113-170338
Katz B, Miledi R (1965) The measurement of synaptic delay, and the time course of ACh release at the neuromuscular junction. Proc R Soc Lond B 161:483–495. https://doi.org/10.1098/rspb.1965.0016
Khan MM, Lustrino D, Silveira WA, Wild F, Straka T, Issop Y, O'Connor E, Cox D et al (2016) Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease. Proc Natl Acad Sci USA 113:746–750. https://doi.org/10.1073/pnas.1524272113
Krnjevic K, Miledi R (1958) Some effects produced by adrenaline upon neuromuscular propagation in rats. J Physiol 141(2):291–304. https://doi.org/10.1038/193041a0
Kuba K (1970) Effects of catecholamines on the neuromuscular junction in the rat diaphragm. J Physiol 211(3):551–570. https://doi.org/10.1113/jphysiol.1970.sp009293
Kuba K, Tomita T (1971) Effects of noradrenaline on miniature end-plate potentials and on end-plate potential. J Theor Biol 36:81–88. https://doi.org/10.1113/jphysiol.1971.sp009557
Legay C (2018) Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms. Ann N Y Acad Sci 1413(1):104–110. https://doi.org/10.1111/nyas.13595
Lin J-W, Faber S (2002) Modulation of synaptic delay during synaptic plasticity. Trends Neurosci 25:449–455
Misra H, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175
Oliver G, Schäfer EA (1895) The physiological effects of extracts of the suprarenal capsules. J Physiol 18(3):230–276
Palop G, Romero AM, Calatayud JM (2002) Oxidation of adrenaline and noradrenaline by solved molecular oxygen in a FIA assembly. J Pharmaceut Biomed 27(6):1017–1025. https://doi.org/10.1016/S0731-7085(01)00610-0
Rodrigues A, Messi M, Wang Z-M, Abba M, Pereyra A, Birbrair A, Zhang T, O’Meara M et al (2019a) The sympathetic nervous system regulates skeletal muscle motor innervation and ACh receptor stability. Acta Physiol 225:e13195. https://doi.org/10.1111/apha.13195
Rodrigues A, Wang Z-M, Messi M, Delbono O (2019b) Sympathomimetics regulate neuromuscular junction transmission through TRPV1, P/Q- and N-type Ca2+ channels. Mol and Cell Neurosci 95:59–70
Rudolf R, Khan MM, Lustrino D, Labeit S, Kettelhut IC, Navegantes LC (2013) Alterations of cAMP dependent signaling in dystrophic skeletal muscle. Front Physiol 4:290. https://doi.org/10.3389/fphys.2013.00290
Schneggenburger R, Neher E (2000) Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406(6798):889–893
Schneggenburger R, Neher E (2005) Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol 15(3):266–274
Soić-Vranić T, Bobinac D, Bajek S, Jerković R, Malnar-Dragojević D, Nikolić M (2005) Effect of salbutamol on innervated and denervated rat soleus muscle. Braz J Med Biol Res 38(12):1799–1805. https://doi.org/10.1590/S0100-879X2005001200008
Straka T, Vita V, Prokshi K, Hörner SJ, Khan MM, Pirazzini M, Williams MPI, Hafner M et al (2018) Postnatal development and distribution of sympathetic innervation in mouse skeletal muscle. Int J Mol Sci 19(7):1935. https://doi.org/10.3390/ijms19071935
Tsentsevitsky AN, Kovyazina IV, Bukharaeva EA, Nikolsky EE (2018) Effect of noradrenaline on the kinetics of evoked acetylcholine secretion in mouse neuromuscular junction. Biochemistry A 12:327–332. https://doi.org/10.1134/S1990747818070012
Tsentsevitsky AN, Khuzakhmetova VF, Bukharaeva EA (2019a) Adrenergic modulation of excitation propagation in peripheral synapses. Biochemistry A 13(3):187–193. https://doi.org/10.1134/S1990747819030097
Tsentsevitsky AN, Kovyazina IV, Bukharaeva EA (2019b) Diverse effects of noradrenaline and adrenaline on the quantal secretion of acetylcholine at the mouse neuromuscular junction. Neuroscience 423:162–171. https://doi.org/10.1016/j.neuroscience.2019.10.049
Acknowledgements
This work was supported by the Russian Science Foundation (Project No. 18-15-00046). The investigation of the catecholamine’s autoxidation was supported by government assignment for FRC Kazan Scientific Center of RAS. We are grateful to Svetlana Dmitrieva for her help in doing the catecholamine’s autoxidation analysis.
Author information
Authors and Affiliations
Contributions
VK and EB contributed equally to the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval
The study conformed to the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, revised 1996) and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other (Int. J. Mol. Sci. 2019, 20, 4860 10 of 17) Scientific Purposes (Council of Europe No. 123, Strasbourg, 1985). The experimental protocol met the requirements of the EU Directive 2010/63/EU and was approved by the Bioethics Committees of Kazan State Medical University (Protocol #3/ 29 Jan 2016).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Khuzakhmetova, V., Bukharaeva, E. Adrenaline Facilitates Synaptic Transmission by Synchronizing Release of Acetylcholine Quanta from Motor Nerve Endings. Cell Mol Neurobiol 41, 395–401 (2021). https://doi.org/10.1007/s10571-020-00840-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-020-00840-3