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In skeletal muscle, does each cell have its own nervous connection, or does a single nerve ending supply a muscle?	Each cell has its own nervous connection so that there is even transmission of action potentials, and excitation-contraction coupling. Though the connections may be from branches of the same nerve, ultimately there are multiple nerves and neuromuscular junctions.
Why is the axon terminal so proximal to the T-tubule?	In order to maximise conduction of the action potential via the neurotransmitter being released directly on to the postsynaptic membrane which generates an action potential in this membrane which instantly travels into the T tubule.
Why is the postsynaptic membrane highly folded?	To maximise its surface area and therefore how many neurotransmitter receptors there are available for binding, and therefore how rapidly the action potential is propagated from the axon to the muscle fibres.
Microscopically, which is the brightest area in a sarcomere?	The I band, which consists only of actin, which is a smaller protein than myosin.
Actin filaments are attached to Z-lines and myosin filaments are attached to M-lines - how are they attached?	They are phyiscally attached to these anchors via connective tissue.
What are the myosin binding sites hidden by?	Tropomyosin.
Titin attaches myosin filaments to the Z lines of the sarcomere. How far throughout the muscle do they extend?	They extend from the individual muscle fibres to the tendon at which the muscle attaches to the bone at its proximal end.
How many strands of myosin intertwine to form a single filament?	Hundreds.
Is crossbridge cycling (myosin head binding to site on actin filament, changing conformation, detaching and re-attaching) a continual process?	Only while Ca2+ is present; when it is removed, the myosin head detaches and the filaments separate.
How does the arrival of the action potential at the neuromuscular junction lead to release of calcium from the sarcoplasmic reticulum?	The action potential causes the release of a neurotransmitter (acetylcholine) which binds to its nicotinic receptor on the postsynaptic membrane of the muscle cell. This results in the opening of ligand-gated ion channels, depolarising the membrane and propagating the action potential across the muscle cell. When the action potential travels down the T tubule (an evagination in the muscle cell membrane), it encounters the dihydropyridine receptor and causes a conformational change in it. This in turn leads to a conformational change in the ryanodine receptor - now the full Ca2+ channel is open and Ca2+ can travel down its concentration gradient from the sarcoplasmic reticulum to the sarcolemma.
What prevents too much calcium being released from the sarcoplasmic reticulum?	Ca2+-ATPase which actively pumps Ca2+ back into the sarcoplasmic reticulum against its concentration gradient.
List 3 functions of ATP in skeletal muscle contraction.	1) Binding of ATP to myosin dissociates cross-bridges (myosin heads) bound to actin, allowing the bridges to cycle their activity. 2) Hydrolysis of ATP by myosin ATP-ase on the heavy chain of the myosin head energises the cross-bridges with actin, providing the energy for force generation. 3) ATP is required by Ca2+-ATPase in the sarcoplasmic reticulum, as its hydrolysis provides the energy to sequester Ca2+ against its concentration gradient (active transport) in order to end contraction.
ATP in the muscle is in limited supply, but is good for providing the initial energy. How long can it fuel maximum exertion for?	2-3 seconds
Creatinine phosphate is a high energy phosphate group, and can therefore provide energy to maintain maximal muscle exertion for longer than the muscle ATP stores. How long can it provide energy for contraction for?	10-12 seconds - an increase of 9-10 seconds.
Anaerobic glycolysis eventually results in fatigue of muscle as energy supplies are depleted. What energy does it use? How long can it support maximal muscle exertion for?	2-3 ATP are gained from glycolysis using blood glucose/muscle glycogen stores, and this can support ~2 minutes of maximum muscle exertion.
The best energy source of all for sustained muscle activity is oxidative phosphorylation. It takes the longest to become fully active, but if the effort being exerted is submaximal, how long can it support exertion for?	Essentially indefinitely as long as enough oxygen is able to be obtained as a H+ acceptor at the end of the electron transport chain. 32 molecules of ATP are produced by glycolysis, the Krebs cycle, and the electron transport chain combined, supporting exertion much more than muscle ATP stores, creatinine phosphate, and glycolysis.
What is the initial trigger for the use of creatinine phosphate in muscle activity/exertion? What does it produce?	Muscle contraction leads to an increased ATP demand, and eventually a decreased ATP supply alongside an increased ADP supply. This increases the activity of metabolic enzymes resulting in an increase in glycolysis and oxidative phosphorylation to produce more ATP, but it also shifts the direction of the following reaction catalysed by creatinine kinase: PCr + ADP <-> Cr + ATP Resulting in the production of more ATP for muscle contraction!
Where does the body obtain creatinine?	In the natural diet, mainly from meat as it is synthesised in the kidney and liver from amino acids, as well as from supplements.
List the following energy sources in order of increasing ability to support muscle activity for long periods of time: glycolysis, muscle ATP stores, oxidative phosphorylation, and creatinine phosphate.	Muscle ATP stores, creatinine phosphate, glycolysis, oxidative phosphorylation.
What supplies most of the ATP when exercising at a low to moderate rate?	Oxidative phosphorylation.
Does lactate cause pain in muscles, allow glycolysis to continue, or both, or neither?	It allows glycolysis to continue. Other factors (e.g. K+ ion production) are thought to induce pain during high intensity/anaerobic exercise.
Which carriers transport the electrons generated in the Krebs cycle to the electron transport chain?	Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD), which are reduced when they carry electrons to the electron transport chain (NADH + FADH2).
Which enzyme converts pyruvate to lactate?	Lactate dehydrogenase.
Under anaerobic conditions, which enzyme recycles NAD+ from NADH + H+?	Lactate dehydrogenase, in the same reaction as converting pyruvate to lactate.
Why is the formation of lactate necessary in anaerobic exercise?	In aerobic conditions, pyruvate is converted to acetyl CoA, but in the absence of O2, the energy production pathway is backed up from the end as intermediates accumulate without the possibility of conversion. This results in pyruvate building up as there is no NAD+ for the oxidation of glucose. The formation of lactate from pyruvate by lactate dehydrogenase provides the energy for oxidising NADH + H+ back to NAD+ so further glycolysis can occur.
What is the Cori cycle?	The process by which lactate can be produced from pyruvate in order to allow glycolysis to continue, but lactate can also be transported to other tissues, predominately the liver where it is used in gluconeogenesis to produce more glucose. This is either delivered to the tissues via the hepatic portal artery for use, or stored as glycogen. Lactate can also be transported from one cell to another in order to be converted back to pyruvate (as pyruvate <-> lactate is a reversible reaction).
At lower intensity exercise, what is the main energy source used by muscles?	Plasma free fatty acids.
At higher intensity exercise, what is the main energy source used by muscles?	Muscle glycogen stores.
Which potential energy substrate is only ever a minor contributor to energy production in exercise?	Protein/muscle triglycerides.
Energy substrates vary differently with regard to exercise duration than with regard to exercise intensity. As exercise intensity increases, there is greater reliance on muscle glycogen. As exercise duration increases, what energy substrate is relied upon to a greater extent?	With increased distance/energy expended, more reliance is on fatty acids than carbohydrates in both males and females.
Do males or females rely more heavily on protein towards the end of an endurance race?	Males do - oestrogen in females encourages fat usage in endurance races, resulting in glycogen conservation (which is also encouraged by lower adrenaline levels). However, males do not conserve glycogen and so this is depleted by the end of an endurance race, and males rely more heavily on amino acids/protein.
What is the 'crossover concept'?	The idea that at around 30% of an individual's VO2 max (which varies between individuals as a result of genetics/ training), there is a crossover to use of carbohydrate as the main energy source rather than fat (which is predominately used in low intensity exercise). Also that after ~20 minutes of exercise, there is a crossover from the use of carbohydrate as a primary energy source to fat as endurance increases.
What is the limitation in fat being used as a main energy source over glycogen (which can lead to exhaustion)?	'Fat burns in a carbohydrate flame': Although fats enter the Krebs cycle as acetyl CoA, they must join with oxaloacetate to form citrate - and oxaloacetate is a product of carbohydrate breakdown. As such, if carbohydrate stores have been depleted, it will not be possible to use fat stores - exhaustion.
What does a motor unit consist of?	An alpha motor neuron (type 1a somatic) and its skeletal muscle fibres (and thus also the neuromuscular junctions). The number of muscle fibres that a motor neuron varies greatly, but the number of axon terminals to muscle fibres is 1:1.
Within a motor unit, do muscle fibre compositions tend to be homogeneous or heterogeneous?	Homogeneous - would not tend to mix fast and slow twitch, for instance.
What is true of the force and fatigue of fast twitch glycolytic muscle fibres?	High force and fast fatigue.
What is true of the force and fatigue of fast twitch oxidative muscle fibres?	Moderate force + fairly fatigue resistant.
What is true of the force and fatigue of slow twitch oxidative muscle fibres?	Low force, highly fatigue resistant.
The three main types of muscle fibre are defined by what?	Their myosin type.
Which sport requires the most slow twitch muscle fibres? And which requires the least?	Skiing requires the most slow twitch muscle fibres, while running 100-200m requires the least (sprinting: fast twitch glycolytic).
What is the myoglobin content in slow twitch oxidative, fast twitch oxidative, and fast twitch glycolytic muscle fibres?	Slow twitch oxidative: high. Fast twitch oxidative: high. Fast twitch glycolytic: low.
What is the capillary density (high or low) in slow twitch oxidative, fast twitch oxidative, and fast twitch glycolytic muscle fibres?	Slow twitch oxidative: high. Fast twitch oxidative: high. Fast twitch glycolytic: low.
What is the mitochondrial density (high or low) in slow twitch oxidative, fast twitch oxidative, and fast twitch glycolytic muscle fibres?	Slow twitch oxidative: high. Fast twitch oxidative: high. Fast twitch glycolytic: low.
What is the myosin ATPase activity (high, intermediate, or low) in slow twitch oxidative, fast twitch oxidative, and fast twitch glycolytic muscle fibres?	Slow twitch oxidative: low. Fast twitch oxidative: intermediate. Fast twitch glycolytic: high.
List some possible reasons for the quick generation of fatigue in fast twitch glycolytic muscles.	They predominately source energy from glycolysis which produces few ATP molecules, the fibres are bigger and have more myosin ATPase with which to break down ATP and deplete stores rapidly, lactate is a product if the O2 supply is limited which limits pyruvate production, strong contractions (as these fibres produce high force) can compress the blood supply to the muscle reducing metabolite delivery, and there can be neuromuscular fatigue of the alpha-motor neurons.
What is a muscle twitch?	A reproducible, all-or-nothing event, which all muscle contractions are comprised of. Although muscle contraction force and duration may vary, the response of a single muscle cell to a single action potential is always the same: muscle twitch. (So, a mechanical response to a single action potential)
The length of a muscle twitch varies between muscle fibre types. What is the range of variation?	From several to hundreds of milliseconds.
There is a type of muscle contraction activity that looks similar to a muscle twitch with regard to duration. What is this?	Blinking!
What is the latent period after the stimulus is detected but before the contraction is started?	It results from the time taken for: processing of the neural input; release of Ca2+ ions from the sarcoplasmic reticulum; and cross-bridge cycling in which there is a brief delay while sufficient strong myosin-actin interactions occur.
What initiates the relaxation phase of the muscle twitch?	Ca2+ reuptake into the sarcoplasmic reticulum.
What are the types of muscle twitch (isotonic or isometric) dependent on?	Whether the muscle can shorten or not. If it can, it is isotonic as it creates a force greater than the force that is opposing it (the load), i.e. lifting a weight. If the muscle cannot shorten, it is isometric as the force applied to the muscle is greater than the force that the muscle can generate - the muscle does not shorten but the force is maintained. (Difficult to imagine: the body of the muscle shortens but the overall length - including the tendons - does not)
What would the plateau of an isotonic muscle twitch represent?	Sufficient force having been generated in order to move the weight that the muscle is contracting against.
Which two factors does the force that a muscle is able to generate depend on?	The force in the individual fibres, and the number of fibres contracting (this is regulated and the body is good at gauging how many fibres are required for a certain amount of force generation).
The force in the individual muscle fibres (which contributes to the overall force that a muscle can generate) is dependent on the number of active crossbridges. What is this influenced by?	The fibre diameter, the frequency of fibre stimulation, and changes in fibre length.
Isometric contractions are only reproducible, all-or-nothing events if there is low frequency stimulation of that muscle cell. In high frequency stimulation, there is high tension developed. What is treppe and how does it develop?	Treppe is an overlap between twitch and contraction - the fibre has a chance to relax but is stimulated to contract again instantly. This results in increased tension, likely as a result of not all the Ca2+ being returned to the sarcoplasmic reticulum so that the next twitch is larger and can contract for longer. This may develop into tetanus if all troponin is constantly occupied by Ca2+ and all myosin is attaching to actin binding sites, resulting in there being no opportunity for Ca2+ to return to the sarcoplasmic reticulum and constant contraction.
The greater the fibre diameter, the greater force it can generate - why? Along these lines, which is the biggest type of muscle fibre?	The more myofibrils you have, the more sarcomeres you have in parallel, the more cross-bridges you can form, and the more tension you can develop. Slow twitch is smaller and fast twitch is larger, because fast twitch fibres can develop greater force and do so more quickly.
What is the length-tension relationship of a muscle fibre?	The optimal length for generating force. If the actin and myosin fibres are completely overlapped, they will not be able to generate any tension as they cannot form further cross-bridges and overlap any more. If the actin and myosin fibres are barely overlapped at all, they will not be able to generate sufficient force by only being overlapped at the ends of the sarcomeres. The muscle generates its maximum force at its resting length because this has the right amount of overlapping of actin and myosin - enough that not much more overlapping needs to occur to generate force, but not so much that further overlapping can't occur.
How does the nervous system exert control over the amount of force generated by a muscle?	By varying the number of fibres recruited.
Structurally, how can muscle fibres differ?	In the number of fibres that they contain (e.g. 5, 10 etc.), and in the diameter (and strength) of fibres that they contain (e.g. all large fast twitch glycolytic or all smaller slow twitch oxidative).
True or false: within any given motor unit, fibres tend to be a similar size.	Generally: true.
True or false: motor units with mainly larger fibres have more fibres.	Generally, yes - so slow twitch have fewer muscle cells.
Given that motor units tend to contain fibres of similar sizes, and if a motor unit contains large fibres it will contain more fibres, how do you think 'the size principle' with regard to recruiting motor units works?	The brain recruits motor units of appropriate sizes for the force required - i.e. it will recruit a small motor unit consisting of a small number of small muscle fibres for a low amount of exertion/tension required. In turn, these will be controlled by a small motor neuron as it needs to synapse on a smaller number of cells that a large motor neuron. Small motor neurons fire first.
What is asynchronous activation?	The process by which the central nervous system recruits different small groups of motor units alternatively in order to sustain long-term contraction and allow groups to recover in order to avoid fatigue.
True or false: in light intensity activity there is similar recruitment of different fibre types, with no one type being recruited more than another?	True
In heavy intensity exercise, when a large amount of force needs to be generated, which muscle fibre type is predominately recruited?	Type IIb/fast twitch glycolytic.
Here is a summary of the components contributing to the generation of force in a muscle.	Image: summaryofmusclecontractioncomponents (image/jpg)
As well as controlling the force generated by a muscle, the body can control how rapidly this force is generated. What is the relationship between force required and latency?	When less force is required, there will be a shorter latency, as fewer motor units need to be recruited, and fewer muscle cells are involved so less time is required for sufficient Ca2+ to be released from the sarcoplasmic reticulum. Oppositely, when a larger force is required, the latency will be longer as more (larger) muscle fibres need to be recruited which takes more CNS processing time and longer to generate sufficient Ca2+ for contraction.
Which would have a shorter latency of force generation: isotonic or isometric contraction?	In isotonic contraction the muscle is able to shorten and the force it generates is greater than the force against it (the load) - therefore, the minimum load would be 0kg and the minimum latency would be possible as so few motor units would need to be recruited. A heavy load that could apply more force to the muscle than the muscle could generate, would result in more (larger) motor units needing to be recruited, and there would be a longer latency period as sufficient Ca2+ was released etc. though the muscle would not shorten (isometric contraction).

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