Human Physiology Laboratory report

Human Physiology Laboratory report (CW1) Proforma

4PHYM001W

Student’s Name:Amirreza Ghasemi Barzegar

Introduction

Descending somatic neurons are two inclining pathways accountable for the given skeletal muscles movement. Any motor order from the primary motor cortex is sent down the axons of the Betz cells to activate upper motor neurons in either the cranial motor nuclei or in the ventral horn of the spinal cord. The axons of the corticobulbar tract are ipsilateral, meaning they project from the cortex to the motor nucleus on the same side of the nervous system. Conversely, the axons of the corticospinal tract are largely contralateral, meaning that they cross the midline of the brain stem or spinal cord and synapse on the opposite side of the body.

Therefore, the right motor cortex of the cerebrum controls muscles on the left side of the body, and vice versa.  Excitation–contraction coupling is the physiological process of converting an electrical stimulus to a mechanical response. It is the link (transduction) between the action potential generated in the sarcolemma and the start of a muscle contraction. Acetylcholine released from the axon terminal binds to receptors on the sarcolemma. An action potential is generated and travels down the T tubule. Calcium anions are released from the sarcoplasmic reticulum in response to the change in voltage. Calcium anions bind troponin; cross-bridges form between actin and myosin. Acetylcholinestrrerase removes acetylcholine from the synaptic cleft. Calcium anions transported back into the sarcoplasmic reticulum. Tropomyosin binds active sites on actin causing the cross-bridge to detach.

ATP first binds to myosin, moving it to a high-energy state. The ATP is hydrolysed into ADP and inorganic phosphate (Pi) by the enzyme ATPase. The energy released during ATP hydrolysis changes the angle of the myosin head into a “cocked” position, ready to bind to actin if the sites are available. ADP and Pi remain attached; myosin is in its high energy configuration. The active site on actin is exposed as calcium anions binds troponin. The myosin head forms a cross-bridge with actin. During the power stroke, the myosin head bends, and ADP and phosphate are released. A new molecule of ATP attaches to the myosin head, causing the cross-bridge to detach. ATP hydrolyses to ADP and phosphate, which returns the myosin to the “cocked” position the muscle contraction cycle, is triggered by calcium ions binding to the protein complex troponin, exposing the active-binding sites on the actin. As soon as the actin-binding sites are uncovered, the high-energy myosin head bridges the gap, forming a cross-bridge.

Once myosin binds to the actin, the Pi is released, and the myosin undergoes a conformational change to a lower energy state. As myosin expends the energy, it moves through the “power stroke,” pulling the actin filament toward the M-line. When the actin is pulled approximately 10 nm toward the M-line, the sarcomere shortens and the muscle contracts. At the end of the power stroke, the myosin is in a low-energy position. After the power stroke, ADP is released, but the cross-bridge formed is still in place. ATP then binds to myosin, moving the myosin to its high-energy state, releasing the myosin head from the actin active site. ATP can then attach to myosin, which allows the cross-bridge cycle to start again; further muscle contraction can occur. Therefore, without ATP, muscles would remain in their contracted state, rather than their relaxed state.

ACh is the neurotransmitter that binds at the neuromuscular junction (NMJ) to trigger depolarization, and an action potential travels along the sarcolemma to trigger calcium release from SR. The actin sites are exposed after Calcium anion enters the sarcoplasm from its SR storage to activate the troponin-tropomyosin complex so that the tropomyosin shifts away from the sites. The cross-bridging of myposin heads docking into actin-binding sites is followed by the “power stroke”—the sliding of the thin filaments by thick filaments. The power strokes are powered by ATP. Ultimately, the sarcomeres, myofibrils, and muscle fibers shorten to produce movement. Anticholinesterases (anti-ChEs) are toxic to humans principally because they interfere with molecular and cellular mechanisms required for the normal functioning of the central nervous system (CNS) and peripheral nervous system (PNS). Their adverse health effects are related mostly to inhibition of acetyl cholinesterase (AChE), a critically important CNS and PNS enzyme that hydrolyse the neurotransmitter acetylcholine (ACh). Chemical-warfare (CW) agents exploit the acute, life-threatening properties of profound AChE inhibition; some of the anti-ChEs precipitate other clinically significant deleterious effects on sensory and neuromuscular function.

Thus, the aim of this experiment were to 1)establish the effect of an organophosphate compound on muscle function, and 2) establish effect of an organophosphate compound on AChE activity. The hypothesis for this week was that 1) each skeletal muscle fibre is controlled by a motor neuron.  2)  Exposure to very low concentrations of AChE inhibitors may induce contractions of bronchial smooth muscle.       

Results

Table 1: RBC AChE Activity (% Untreated Animal Samples)

Table 2: Effect of Organophospate exposure on Muscle Grip Strength as a function of time

Graph Mean Average of the Effects of Organophospate exposure on Muscle Grip Strength as a function of time

The study was carried out on 6 rats all previously untreated with the organophosphate compound. From the results, it was clear that The AChE activity decreased after administration of the second dose showing that AChe contributes to the long-term effects of OP intoxication and neurobehavioral deficits. The second test carried out to determine the effects of exposure to organophosphates on muscle grip strength as function of time showed that after administering the 2 doses each animal began to show a gradual decrease in muscle activity. This is because Organophosphates work by preventing AChe actions causing immoderate stimulation of nicotinic and muscarinic receptors. This, therefore, affirms the fact that the acute effects of organophosphate exposure can indeed persist for more than 5 years with their slow gradual harmful effects on skeletal muscle grip and strength seen with the treatment time-point frame.

Discussion

Reversible AChE inhibitors play an important role in pharmacological manipulation of the enzyme activity. These inhibitors include compounds with different functional groups (carbonate, quaternary or tertiary ammonium group), and have been applied in the diagnostic and/or treatment of various diseases such as: myasthenia gravis, AD, post-operative ileus, bladder distension, glaucoma, as well as antidote to anticholinergic overdose.

Muscle contraction usually stops when signalling from the motor neuron ends, which repolarizes the sarcolemma and T-tubules, and closes the voltage-gated calcium channels in the SR. Calcium ions are then pumped back into the SR, which causes the tropomyosin to (or re-cover the binding sites on the actin strands. A muscle also can stop contracting when it runs out of ATP and becomes fatigued.

Organophosphates work by hindering the action of AChE. This causes immoderate stimulation of muscarinic and nicotinic receptors at the postsynaptic membrane. ACh binds to the endplates of smooth muscles and secretory glands causing nausea, vomiting, bronchospasm, meiosis, blurry vision, bronchorrea, and sialohorrea. Nicotinic effect on skeletal muscle can cause fasciculation and flaccid paralysis. Nerve gas poisoning can vary in severity from mild to moderate or severe.

From major reports, is that the rat adequately imitates responses of humans to exercise in those basic blood biochemical parameters reported here. The resemblance of rat and human physiologically blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified.