**5. Conclusion**

*Adenosine Triphosphate in Health and Disease*

at all) [54–56].

mia [64].

from 10 to 35°C, the size of non-quantum secretion has two relative peaks at 20 and 35°C and two minima at 25 and 10°C (in the latter case, the H effect is not expressed

The frequency of spontaneous single-quantum responses in synapses of warmblooded animals increases as the temperature increases [56–58] without changing the amplitude of these responses [59]. Thus, two processes of acetylcholine release, namely quantum and non-quantum, have a different temperature dependence,

The analysis of the published data leads to an unequivocal conclusion about the rise of the synaptic delay of postsynaptic responses with decreasing temperature on

It is known that in the neuromuscular synaptic cleft, there is an acetylcholinesterase which rapidly cleaves the neurotransmitter acetylcholine [62]. It was shown that when the temperature of the rat diaphragm preparation was reduced from 37 to 17°C, the activity of acetylcholinesterase decreased by 34% [63]. A similar pattern was observed in experiments with the preparation of the frog sartorius muscle which led to a suggestion that a decrease in the activity of acetylcholinesterase is responsible for an increase of the time course of the end-plate current at hypother-

To study the state of postsynaptic cholinergic receptors, cholinomimetics (primarily the slowly decaying cholinomimetic agent—carbachol) and cholinolytics are used. In experiments with slow muscle preparations such as rat m. soleus, the amplitude of the miniature potentials of the terminal plate did not change after application of carbachol at a temperature range from 18 to 38°C. On the other hand, at temperatures 37–38°C, there was a 40% decrease in the incidence of spontaneous postsynaptic responses in the presence of this cholinomimetic (in which combina-

There are several studies on the temperature dependence of the contractile apparatus of "slow" skeletal muscles with conflicting data on the muscles of the same animals [66–70]. Thus, according to some sources, the temperature dependence of the "slow" muscle fibers of the rat is much more pronounced than the "fast" ones [42, 71–79], while others found that the temperature sensitivity of the myosin of the

In experiments on demembranized muscle fibers, where the temperature effects

We found that as the temperature is lowered, the force of contractions of the slow skeletal muscle of the rat increases [38], while the fast one decreases. With carbachol-induced contraction (when only receptors of the postsynaptic membrane are stimulated), as the temperature decreases, the amplitude of contractions of the

It is known that a decrease in Ca2+ concentration, which provides exocytosis of the neurotransmitter quanta [82–84], reduces the strength of the contraction of the skeletal muscle over time—in contrast to the rapid effect on cardiomyocytes [85]. This action is temperature-dependent; in rat fast muscle fibers, the contraction force increased with increasing concentration of calcium ions; the lower the temperature,

the more is the effect. A rat slow muscle did not produce similar effect [86].

"slow" muscle fibers of the rat does not differ from the "fast ones" [80, 81].

of electromechanical coupling are not relevant and only the modulation of the mechanical function itself plays a role, it was clarified that the dependence of the reduction force of "slow" and "fast" fibers on temperature is similar [80]. With an increase of temperature from 10 to 35°C, the force of contraction of "slow" fibers increased threefold and the "fast" ones by three and a half. The situation is different with the rate of contraction. Thus, the rate of reduction of "fast" fibers increased with increasing temperature from 10 to 35°C, while for "slow" fibers this parameter

which indicates the presence of independent mechanisms [55, 58].

rodent preparations [60, 61]—the same as in cold-blooded.

tion indicates presynaptic nature of the effect) [65].

changed insignificantly [80].

slow muscle of the rat also increases [38].

**16**

Despite a large number of studies, the direct mechanisms of temperature effects on the functioning of the muscle remain unsolved [87, 88]. Moreover, if the muscle is stimulated directly, then the temperature change no longer has such an effect. That is, the reason for the phenomenon being discussed is synaptic.

It was believed that changes in motor units at low temperature are due to depletion of the activity of metabolic enzyme systems [30, 31] or energy synthesis and transfer processes [89, 90]. However, it was clear that the contribution of the temperature sensitivity of the muscle biochemical processes cannot justify such dramatic changes in the nature of the contraction of the whole muscular organ with a change in temperature [91]. We suggest that the temperature-sensitive tonic effects of endogenous ATP during the contraction can underlie the phenomenology of changes in muscle responses with decreasing temperature.

In conclusion, we believe that studying the effects of hypothermic conditions has not only theoretical significance but also potentially important clinical implications since hypothermia is widely used in clinical practice for cerebral protection during surgical interventions or resuscitation of critically ill patients [92–96]. This underlines the importance of studying the reaction of other organs and tissues to hypothermia and especially the effect that low temperatures have on receptor-based interactions. Such studies add important information regarding the activity of P2 receptors under hypothermic conditions in mammalian muscles. Although these results cannot be directly transferred to human muscle tissues, they provide important insight into how activation of human P2 receptors might behave under hypothermia and predict how effects of certain drugs might be altered by this nonphysiologic state.
