The Participation of Presynaptic Alpha7 Nicotinic Acetylcholine Receptors in the Inhibition of Acetylcholine Release during Long-Term Activity of Mouse Motor Synapses

Abstract

In the motor synapses of the mouse diaphragm, we recorded the miniature endplate potentials (MEPPs) and multiquantal endplate potentials induced by stimulation of the phrenic nerve (EPPs). Prolonged continuous rhythmic stimulation (50 Hz for 40 seconds) caused a depression of the synaptic transmission in the form of a gradual biphasic decrease in the quantal content of EPPs in the train. A rapid decrease in the quantal content of the EPPs to 50% of the amplitude of the first EPPs in the train (EPP1) during the first 10 seconds of activity was followed by a slower decrease in the EPP quantum content to 35–40% of EPP1 by the 40th second of stimulation. Blockage of the α7 nicotinic acetylcholine receptors by methyllycaconitine (20 nM), as well as ryanodine receptors by ryanodine (3 µM), or small-conductance calcium-activated potassium channels of the SK-type by apamin (1 µM) significantly reduced the development of depression; the EPP quantal content decreased to 65–70% of EPP1 by the 10th second of stimulation and maintained at this level for the next 30 seconds of stimulation. It was concluded that in mouse cholinergic motor synapses, the mechanism of transient depression of transmission may be autoinhibition of acetylcholine quantal secretion by endogenous acetylcholine/choline, which activates the α7 nicotinic acetylcholine receptors and triggers the signaling cascade that involves presynaptic ryanodine receptors and SK channels.