Activation of Neuronal Nicotinic Receptors Inhibits Acetylcholine Release in the Neuromuscular Junction by Increasing Ca2+ Flux through Cav1 Channels

Abstract

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse. ACh release was assessed by electrophysiological methods. Changes in calcium transients were recorded using a calcium-sensitive dye. Nicotine hydrogen tartrate salt application (10 μM) decreased the amount of evoked ACh release, while the calcium transient increased in the motor nerve terminal. Both of these effects of nicotine were abolished by the neuronal ACh receptor antagonist dihydro-beta-erythroidine and Cav1 blockers, verapamil, and nitrendipine. These data allow us to suggest that neuronal nicotinic ACh receptor activation decreases the number of ACh quanta released by boosting calcium influx through Cav1 channels.

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

“…Neuromuscular synapses of vertebrates contain presynaptic AchRs, which implement a modulatory action of ACh on its own release. Despite a long history of studies showing the effects of both AChR activators and blockers on quantal ACh secretion [ 23 , 24 , 25 , 26 , 27 , 28 ], there is still no consensus on the role of presynaptic ionotropic nicotinic (nAChR) and metabotropic muscarinic (mAChRs) receptors at the motor-nerve terminals in modulation of the kinetics of evoked ACh release. The data about the effects of nAChR blocker d-tubocurarine [ 29 ] and muscarinic agonists on the synaptic delays in the neuromuscular junctions [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ] suggest the participation of AChRs in regulation of the time course of ACh release.…”

“…There are a large amount of data about the effects of nAChRs agonists and antagonists on the ACh quanta number released in response to nerve stimulus [ 23 , 25 , 26 ]. Nevertheless, the results of the investigations about changes in the kinetics of ACh quanta release under specific nAChR modulation are scarce.…”

“…As an alternative option for the nAChR participation in the regulation of the secretion kinetics, we have to take into account that nAChRs can be differentially coupled to Ca 2+ -induced Ca 2+ release and/or voltage-gated Ca 2+ channels. Ca 2+ input through nAChRs can positively modulate the activity of L-type Ca 2+ channels in the neuromuscular junctions [ 26 , 55 ]. This type of Ca 2+ channel is responsible for a higher degree of secretion asynchrony in the neuromuscular synapses of newborn rats [ 52 , 56 ] as well as at adult frog neuromuscular junctions [ 57 ].…”

Fluorescently Labeled α-Conotoxin TxID, a New Probe for α3β4 Neuronal Nicotinic Acetylcholine Receptors

“…Nicotinic acetylcholine receptors (nAChRs) are transmembrane ligand-gated ion channels, which are widely distributed in the central and peripheral nervous systems of primitive and evolutionary advanced organisms [ 1 , 2 ]. As a member of the ligand-gated ion channel family, nAChRs play a vital role in regulating signal transmission between nerve and muscle [ 3 ].…”

Light-Controlled Modulation and Analysis of Neuronal Functions

“…In the work by Zhilyakov et al, the authors reported the results from their investigation on the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release and the changes in the concentration of presynaptic calcium levels [ 61 ]. For this purpose, they used a pharmacological approach, electrophysiological techniques, and a method for the optical registration of changes in calcium levels in the motor nerve endings.…”