Abstract
A review of the data on the modulatory action of adenosine 5’-triphosphate (ATP), the main co-transmitter with acetylcholine, and adenosine, the final ATP metabolite in the synaptic cleft, on neuromuscular transmission is presented. The effects of these endogenous modulators on pre- and post-synaptic processes are discussed. The contribution of purines to the processes of quantal and non-quantal secretion of acetylcholine into the synaptic cleft, as well as the influence of the postsynaptic effects of ATP and adenosine on the functioning of cholinergic receptors, are evaluated. As usual, the P2-receptor-mediated influence is minimal under physiological conditions, but it becomes very important in some pathophysiological situations such as hypothermia, stress, or ischemia. There are some data demonstrating the same in neuromuscular transmission. It is suggested that the role of endogenous purines is primarily to provide a safety factor for the efficiency of cholinergic neuromuscular transmission.
Highlights
The neuromuscular junction of vertebrates is the most well-studied cholinergic synapse
After several types of purine receptors had been cloned, it was suggested that adenosine -triphosphate (ATP) receptors should be divided into two families based on their molecular structure and activation mechanism: P2X receptors are ligand-gated ion channels and P2Y receptors are G protein-coupled receptors
We found that in rat soleus muscle the presynaptic inhibitory effect of exogenous ATP decreased exponentially until it completely disappeared at 14 ◦C, while at postsynaptic level ATP had no effect at normal temperature, but at low temperature, it potentiated the carbachol-induced contractions [76]
Summary
The neuromuscular junction of vertebrates is the most well-studied cholinergic synapse. After several types of purine receptors had been cloned, it was suggested that ATP receptors should be divided into two families based on their molecular structure and activation mechanism: P2X receptors are ligand-gated ion channels and P2Y receptors are G protein-coupled receptors This classification has been universally approved and to date, seven subtypes of P2X- (P2X1–7) and eight subtypes of P2Y receptors (P2Y1,2,4,6,11-14) have been described [12,13]. It has been established that ATP, without being degraded, can actively regulate the effectiveness of neuromuscular transmission [16,21,22,23,24,25], modulating the quantal and non-quantal release of the main transmitter which is ACh. ATP as a co-transmitter accompanies a number of classical neurotransmitters, such as ACh, GABA, glycine, and glutamate [26], and is released upon activation of the presynaptic membrane into the synaptic cleft from the vesicles [27] or through some other physiological mechanisms [28]. The regulation of ATP and adenosine degradation is considered to be a novel mechanism to regulate skeletal muscle activity [29] this needs to be developed further
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