The Mechanism of Choline-Mediated Inhibition of Acetylcholine Release in Mouse Motor Synapses

Abstract

The mechanism of action of tonically applied choline, the agonist of α7 nicotinic acetylcholine receptors (nAChRs), to the spontaneous and evoked release of a neurotransmitter in mouse motor synapses in diaphragm neuromuscular preparations using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) was studied. Exogenous choline was shown to exhibit a presynaptic inhibitory effect on the amplitude and quantal content of EPPs for the activity of neuromuscular junction evoked by single and rhythmic stimuli. This effect was inhibited either by antagonists of α7-nAChRs, such as methyllycaconitine and α-cobratoxin, or by blocking SK-type calcium-activated potassium (KCa) channels with apamin or blocking intraterminal ryanodine receptors with ryanodine. A hypothesis was put forward that choline in mouse motoneuron nerve terminals can activate presynaptic α7-nAChRs, followed by the release of the stored calcium through ryanodine receptors and activation of SK-type KCa channels, resulting in sustained decay of the quantal content of the evoked neurotransmitter release.

Metabotropic GABAB receptors mediate GABA inhibition of acetylcholine release in the rat neuromuscular junction

“…) or evoked release (Gaydukov et al . ; Thyagarajan et al . ) were revealed, as well as the mechanisms of the opposite regulation of these forms of quantal neurotransmitter release (Pan et al .…”

“…However, to date a number of experimental facts have accumulated indicating the possibility that spontaneous and evoked forms of neurotransmission are independent neuronal signal transduction pathways (Ramirez and Kavalali 2011;Walter et al 2014). Therefore, specific mechanisms of selective regulation of solely spontaneous (Taniguchi et al 2000;Glitsch 2006;Pratt et al 2011) or evoked release (Gaydukov et al 2014;Thyagarajan et al 2014) were revealed, as well as the mechanisms of the opposite regulation of these forms of quantal neurotransmitter release (Pan et al 1996;Wasser et al 2007). Furthermore, data were obtained suggesting that the processes of spontaneous and evoked quantal release of the neurotransmitter may differ by molecular fusion mechanisms (De ak et al 2006;Maximov et al 2007;Zhou et al 2013) or by spots of quanta released within the boundaries of the same synapse (Ramirez and Kavalali 2011;Melom et al 2013).…”

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors

“…Our finding of muscle type nAChR inhibition by Cro demonstrates the postsynaptic activity of this toxin, although the block of hα7 nAChR by Cro may contribute to its presynaptic activity as the participation of α7 nAChR in acetylcholine release in mouse motor synapses was suggested [42]. …”

CaMKII Is Involved in the Choline-Induced Downregulation of Acetylcholine Release in Mouse Motor Synapses

“…All the experiments were conducted at room temperature of 20–22°C. Dissection of the neuromuscular preparation of the left half of the diaphragm with the phrenic nerve was performed according to the earlier described standard protocol [ 4 ]. Miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) upon stimulation of the phrenic nerve were recorded using intracellular glass microelectrodes filled with 2.5 M KCl (the resistance at the microelectrode tip was 15–20 MΩ).…”

“…Therefore, these ambiguous consequences of presynaptic alpha7-nAChR activation in various types of synapses pose an important challenge that remains poorly studied. We have established recently that choline (0.1 mM) downregulates the evoked ACh release in mouse neuromuscular synapses via Ca 2+ -dependent Ca 2+ efflux from the store through ryanodine receptors and the activation of the SK-type KCa channels of terminals, resulting in downregulation of ACh release [ 4 ]. Meanwhile, it was unclear whether Ca 2+ -dependent enzymes, such as protein kinase C (PKC) and/or calcium-calmodulin-dependent protein kinase type II (CaMKII), are involved in this cascade.…”