Page 196 - Anatomy and Physiology of Farm Animals, 8th Edition

Microscopic Anatomy and Physiology of Muscle / 181

whole‐animal basis, resistance to fatigue acetylcholinesterase inactivates the ACh.
This enzyme, which degrades ACh, is
entails some poorly defined factors such as
VetBooks.ir motivation. The factors contributing to found within the area of the neuromuscular
junction. Agents that are capable of inhib-
fatigue of an individual muscle fiber have
been best studied in muscle cells in isolated iting the action of the acetylcholinesterase
in vitro preparations outside of the body. enzyme are referred to as anticholinest-
These studies indicate that fatigue is a erases. The effect of anticholinesterases at
function of the muscle cell itself and is not the neuromuscular junction is to prolong
due to failure or fatigue of the neurons that the availability and effects of the ACh.
innervate skeletal muscles. These actions may be desirable in
At the individual cell level, one contribu- some disease states, and neostigmine and
tor to fatigue is a decrease in the availability physostigmine are commonly used anti-
of ATP, as its use increases with increased cholinesterase drugs. However, too much
muscle contractions. However, even with anticholinesterase activity can produce a
strenuous prolonged exercise ATP is never toxicity characterized by muscular spasms
totally depleted, because the intracellular and asphyxiation due to spasms of skeletal
generation of ATP is also increased during muscles necessary for respiration. The
exercise. Increases in intracellular concen- signs of anticholinesterase toxicity also
trations of various metabolites generated include constriction of the pupil of the eye,
as a result of contraction also contribute to intestinal cramps, vomiting, and diarrhea.
fatigue. Among these are the phosphate These signs are due to the increased avail-
from the splitting of ATP to ADP and ability of ACh at neural synapses within
organic acids such as lactic acid. Lactic the parasympathetic division of the auto-
acid can diffuse out of the cell and reduce nomic nervous system. Parasympathetic
the pH of the interstitial fluids within a nerves are discussed in more detail in
muscle. Accumulations of lactic acid within Chapter 11.
muscles contribute to pain and soreness of Anticholinesterase activity is the basis
muscles following strenuous exercise. for some effective insecticides and the
The rate at which ATP is generated so‐called “nerve gases” that have been
within an exercising muscle depends on studied extensively by the armed forces
the availability of substrates for the differ- since World War II. Most of these com-
ent metabolic pathways that produce ATP. pounds are alkyl phosphates, and the
If a muscle primarily uses the glycolytic insecticides are also known as organic
pathway, glucose must be readily available. phosphates or organophosphates. The
Glucose may be stored within the muscle insecticides include such products as
cell as glycogen or delivered via the circula- malathion, parathion, and diazinon.
tion. If a muscle uses the oxidative pathway Products for both external application
to produce ATP, oxygen must be available and oral administration are included
in addition to fatty acids or other similar in the organophosphate insecticides.
substrates. The oxygen, of course, must If improperly used, any of the organo-
arrive via the circulation. Adequate blood phosphates is extremely dangerous, not
flow during exercise to deliver oxygen, only to domestic animals but also to the
fatty acids, and/or glucose to skeletal mus- person using it. Therefore, it is impera-
cle is a key factor in resisting fatigue. tive that this class of insecticides be used
under proper supervision and that
instructions for use are followed exactly.
Drugs That Affect Skeletal Muscle Another group of drugs affecting the
Function neuromuscular junction are the curariform
drugs. These drugs act like curare, the
Almost as soon as ACh initiates the deadly poison that some wild game hunt-
impulse for muscle contraction, the enzyme ing Indians in South American use on