BMS 130 Muscles/Neurons & Action Potentials

1) cell is hypertonic to solution 2) cell is hypotonic to solution 3) cell is isotonic to solution

A red blood cell is in an aqueous solution. Comment on the osmolarity of the cell and solution if: 1) the cell is increasing in size, 2) the cell is decreasing in size, 3) the cell is not changing shape.

Major neurotransmitter in the PNS; released from motor nerves that supply skeletal muscle and from parasympathetic nerves that supply smooth muscle, cardiac muscle, and exocrine glands; also acts in the CNS

Acetylcholine

67% of body fluids; 40% of body weight

Approximately how much of our body is intracellular fluid?

All virtually the same since cells secrete fluid to provide a constant environment for operations.

Are all intracellular fluid the same? Why are they the same or why are they different?

excitatory neurotransmitter in CNS

Aspartate

Botulinum toxin prevents the release of acetylcholine at the synaptic terminals of muscle cells and prevents an action potential in the sarcolemma from occurring, thus causing muscle paralysis. By inhibiting acetylcholinesterase, acetylcholine will not be degraded and allow to continue acting on nicotinic receptors, thus strengthening both voluntary and involuntary muscles in patients with myasthenia gravis. Neuromuscular blocking agents are competitive antagonists of acetylcholine receptors. Particularly, they prevent binding of acetylcholine to nicotinic receptors and prevent the development of neural end plate potentials.

Based on the molecular mechanism of action potential transportation in neuromuscular junction, why do you think botulinum toxin could be used to treat sleep bruxism? And why do you think acetylcholinesterase inhibitor could be used to treat myashthenia gravis? And why do you think neuromuscular blocking agents could be used during the surgery?

Calcium channel blockers (dihydropyridine) slow the movement of Ca2+ into the cells of the heart and blood vessel walls, making it easier for the heart to pump blood as blood vessels relax, thus decreasing blood pressure (heart doesn't have to work as hard).

Based on the molecular mechanism of muscle contraction, why do you think calcium blockers could be used to treat hypertension?

When the action potential in neuron reaches presynaptic membrane, the voltage-gated calcium channels on the pre-synaptic membrane open, and there is an influx of Ca2+ ions. This increase in Ca2+ causes vesicles containing acetylcholine to move to the pre-synaptic membrane. These vesicles fuse with the membrane, and acetylcholine is released into the synaptic cleft. Acetylcholine then binds to nicotinic receptors on the post-synaptic membrane, leading to an influx of Na+ and an efflux of K+ (depolarization, caused by end-plate potential). The membrane potential change activates Na+ channels, eventually creating an action potential in muscles. This ends when acetylcholinesterase degrades acetylcholine to choline, which is uptaken by pre-synaptic membrane. Acetylcholine transferase synthesizes it back to acetylcholine. (Acetylcholine removed = stop in muscle action potential)

Can you describe how a motor neuron's action potential causes a muscle cell to generate an action potential on molecular biological level? Important steps: How does the presynaptic membrane release acetylcholine? How does acetylcholine activate the postsynaptic membrane to generate action potential? How does acetylcholine get breakdown and reuse?

Myosin heads are an ATPase and can cleave ATP to crank back myosin head. Then, the myosin head binds to the active site on the actin filament (this is called cross-bridge formation). This triggers the release of energy in the myosin head. This induces the power stroke, in which the myosin head launches towards the M-line and pulls the thin filament along with it (this is the power stroke). Combining of power strokes leads to sliding of the thin filament along the thick filament. The ADP+P leaves the myosin head, and a new ATP molecule binds. This causes the detachment of the myosin head from the active site. ATP is once again cleaved, and the myosin head is cranked and ready for the next power stroke. Once the lower motor neuron stops, action potentials end, and Ca2+ reenters the sarcoplasmic reticulum via calcium pumps that use ATP. The troponin returns to its original shape (C-subunit no longer bound to Ca2+). Muscle relaxes.

Can you describe the whole process of muscle contraction on molecular biological level? Explain from action potential travels along sarcolemma. Important steps: How does calcium release from sarcoplasmic reticulum? How does cross-bridge formation happen? What is power stroke? How does muscle contraction stop?

The muscle fiber is a single muscle cell; the sarcoplasm is the cytoplasm of muscle cells (filled with myofibrils). Myofibrils are the basic rod-like structures that comprise muscle cells. The thin filament is actin, which the myosin (thick filament) moves along. The sarcomere is a single unit of contraction. Each sarcomere are separated by Z discs, which contain only actin. The M line is where myosin binds. The I band is the region between A bands, and is split by a Z disc (this shrinks during contraction). The A band is where actin and myosin overlap, and the H zone is in the middle of the A band and is split by the M line (this shrinks during contraction).

Can you draw and describe the microanatomy of muscle fiber? Label and explain the following terms: muscle fiber, muscle cell, sarcoplasm, myofibril, thin filament, thick filament, sarcomere, M line, Z discs, I band, A band, H Zone/H band, myosin, actin.

Slow oxidative fibers are slow twitch muscular fibers, and fast oxidative and fast glycolytic fibers are fast twitch muscle fibers. This classification is based on the speed of contraction, and the metabolic pathway used to make ATP. The predominant muscle fiber determines the muscle's function. Slow twitch fibers hydrolyze ATP slowly, and fast twitch fibers hydrolyze ATP quickly. slow oxidative fibers (Type I, "slow red muscle fibers," or slow-twitch muscle fibers): Relatively small fibers and produce weakest contractions because they have the fewest sarcomeres, but they have a lot of blood supply (brings O2). Their sarcoplasm is rich in mitochondria and myoglobin (binds and stores O2). Generate 38 ATP from aerobic respiration. They have low glycogen storage, and can sustain muscle activity for long periods of time. Fast oxidative muscle fibers (Type 2a muscle fibers, or "fast red muscle fibers"): Larger than slow oxidative fibers and have more sarcomeres, so they're stronger. They too have a lot of blood supply and are rich in myoglobin as well as mitochondria. They use ATP more quickly than oxidative phosphorylation can run, so they can also use anaerobic glycolysis (100x faster, but less ATP). Stores glycogen, but fatigues quickly because glycogen is used up readily. Fast glycolytic fibers (Type IIx or "white muscle fibers"): These fibers are the largest and the strongest of the three. Because these fibers use anaerobic glycolysis, they don't rely on oxygen, and thus have fewer blood vessels. Their sarcoplasms have few myoglobin and mitochondria. There are plenty of glycogen reserves in the sarcoplasm to ensure there is plenty of glucose available during contraction. These reserves are used up quickly, so these fibers fatigue the fastest. These are effective in exercises that are short and intense (e.g. sprinting).

Can you tell the differences between slow oxidative fibers, fast oxidative fibers and fast glycolytic fibers?

Isotonic contraction: the tension is the same, but the length changes (e.g. moving object with the same force) Isometric contraction: Same length, but tension changes (e.g. moving heavy object)

Can you tell the differences of isotonic contraction and isometric contraction?

The change in membrane potential of the muscle fiber (graded potential)

Define end-plate potential

The refractory period is a time during an action potential where a second action potential cannot occur.

Define the refractory period.

Depolarization: decrease in potential; membrane less negative Repolarization: return to resting potential after depolarization Hyperpolarization: increase in potential; membrane more negative Resting Membrane Potential: membrane potential of excitable cells between action potentials

Define: Depolarization, Repolarization, Hyperpolarization, Reverse Polarization, Resting Membrane Potential

Stronger stimuli generate a higher frequency of action potentials, causing more neurons in a region to reach threshold

Describe how stimuli of different strengths alters the nerve impulse (action potentials).

The propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials.

Describe saltatory conduction.

Depolarization: Na+ influx Repolarization: K+ efflux Hyperpolarization: K+ continues to diffuse out of the cell Resting Membrane Potential: 2K+ pumped in and 3Na+ pumped out

Describe the flux of Na+ and K+ for each situation above.

Water flows in the direction of the higher tonicity area in order to balance the tonicity, but the cell requires an ideal volume, so it either expands or shrinks in response to the change in the amount of water in the cell.

Describe the process by which the cell is changing shape, in the previous question.

Muscarinic receptors can be found on cardiac muscles cells. Activation of ACh activates G protein-coupled receptors, which are G protein-coupled receptors, lead to the opening of K+ channels. Efflux of K+, due to the concentration gradient, causes the cardiac cell to hyperpolarize. Hyperpolarization inhibits the excitation of cardiac cells which can lead to bradycardia.

Describe the series of events that occurs after ACh binds to its receptor on cardiomyocytes.

When ACh binds to and activates nicotinic receptors, which are ligand-gated ion channels, this directly increases the permeability of cations, both Na+ and K+. There is a net influx of Na+ and a net efflux of K+ based on concentration, but the flux of Na+ is greater than that of K+ so there is a net influx of positive charge into the muscle cell leading to depolarization. This is partially due to the higher affinity of the channel to Na+ and the electrical gradient. The depolarization of the muscle cell caused by activation of nicotinic receptors leads to muscle contraction.

Describe the series of events that occurs after ACh binds to its receptor on skeletal muscle fibers.

The percentages given here will vary between individuals and a major contributor to this difference is the number and size of skeletal muscle cells and adipocytes. Muscle cells contains higher amounts of fluid compared to adipocytes and adipocytes contains significantly lower amounts of fluid compared to other cell types because most of their intracellular content is lipids.

Do all cells have the same amount of intracellular fluid? What factors affect the amount of intracellular fluid in a cell?

executive function, motor control, motivation, arousal, reinforcement, and reward

Dopamine

increases cardiac output and raises glucose levels in the blood

Epinephrine

Primary inhibitory neurotransmitter in brain; often acts in same circuits as glutamate

Gamma-aminobutyric acid (GABA)

Equilibrium potential is the membrane potential where the net flow through any open channel is zero. This is significant as the equilibrium potential determines reaction equilibrium constants and concentration potentials of different ions.

Give a simple definition of the equilibrium potential. What is the significance of the equilibrium potential?

Primary excitatory neurotransmitter in CNS; important in pathways involved with memory and learning

Glutamate

Primary inhibitory neurotransmitter in spinal cord and brain stem

Glycine

promotes wakefulness and orchestrates disparate behaviors and homeostatic functions

Histamine

Plasma (1/5 of ECF), Interstitial fluid (4/5 of ECF), Minor ECF (Lymph and Transcellular fluid)

How are extracellular fluids compartmentalized?

Extracellular fluid is located outside of cells, while intracellular fluid is located within cells.

How are intracellular fluid and extracellular fluid different? (location, not composition)

Down-regulation of carriers

How can you decrease the transport maximum?

Up-regulation of carriers

How can you increase the transport maximum?

If the cell fires twice but quickly in secession, then the summation of the depolarization is sufficient to reach threshold and an action potential is triggered (temporal summation)

How does changes to firing of Ex1 reach threshold potential?

Higher concentration gradient of substance, greater rate of net diffusion; thicker membrane, lower rate of net diffusion; greater surface area of membrane; greater rate of net diffusion; greater lipid solubility of molecule, greater rate of net diffusion; greater molecular weight; lower rate of net diffusion

How does each factor affect the rate of diffusion across the membrane?

Z discs attached to the thin filament gets pulled towards the M line, whole sarcomere gets shorter, A band does not change, H band and I band shorten

How does the microanatomy of sarcomere change when muscle contracts?

Neurotransmitter-bound ligand-gated ion channels: the neurotransmitter activates a ligand-gated ion channel allowing for the opening of the channel and increase in ion flux. The ligand in this case is the neurotransmitter. Neurotransmitter-free ligand-gated ion channel: the neurotransmitter binds to a receptor which activates G-protein, thus this is referred to as G-protein coupled receptors. This complex will directly activate specific ion channels. The complex can also activate an effector protein and it is the effector protein that activates the ion channel.

How is a neurotransmitter-bound ligand-gated ion channels different from a neurotransmitter-free ligand-gated ion channel?

The receptors to which the neurotransmitter binds have different functions and are located on different types of cells.

How is it possible for one type of neurotransmitter to initiate two different effects?

Osmolarity is the concentration of a solution expressed as solute particles per liter.

How is osmolarity different than concentration?

Saltatory conduction takes place in myelinated axons, which allow action potentials to occur only at nodes of Ranvier. Continuous conduction takes place along the entire length of unmyelinated axons (slower velocity).

How is saltatory conduction different from contiguous conduction?

The amount of neurotransmitter that is released is dependent on the frequency of action potentials, with higher frequency resulting in more neurotransmitters being released.

How is the amount of neurotransmitter release at the axon terminal determined?

The pre-synaptic membrane is the membrane of the terminal of the lower motor neuron, and the post-synaptic membrane is the sarcolemma, and the synaptic cleft is the space between them. The motor-end plate The motor-end plate is another name for the synapse. When the action potential in neuron reaches presynaptic membrane, the voltage-gated calcium channels on the pre-synaptic membrane open, and there is an influx of Ca2+ ions. This increase in Ca2+ causes vesicles containing acetylcholine to move to the pre-synaptic membrane. These vesicles fuse with the membrane, and acetylcholine is released into the synaptic cleft. Acetylcholine then binds to nicotinic receptors on the post-synaptic membrane, leading to an influx of Na+ and an efflux of K+ (depolarization, caused by end-plate potential). The membrane potential change activates Na+ channels, eventually creating an action potential in muscles. This ends when acetylcholinesterase degrades acetylcholine to choline, which is uptaken by pre-synaptic membrane. Acetylcholine transferase synthesizes it back to acetylcholine. (Acetylcholine removed = stop in muscle action potential)

If I give you an illustration of neuromuscular junction, can you label and explain the following terms: presynaptic membrane, postsynaptic membrane, motor end-plate, synaptic cleft, voltage-gated calcium channel, calcium ion, synaptic vesicle, acetylcholine, choline, acetylcholinesterase, acetylcholine transferase, nicotinic receptor, sodium ion, potassium ion, depolarization, end-plate potential, voltage-gated sodium ion channel, and action potential?

The sarcolemma is the cell membrane of muscle cells. The sarcolema creates T-tubules that project into the muscle fiber. The sarcoplasmic reticulum is a specialized type of smooth ER in myocytes. The sarcoplasmic reticulum harbors Ca2+ ions and runs parallel to T-tubules. Tropomyosin is a string-like protein that wraps around F-actin, covering its active sites to prevent myosin heads from binding. Troponins are smaller and are made up of three subunits (T --> binds tropomyosin, I --> binds F-actin, and C--> binds to Ca2+ ions). Dihydropyridine receptors are stimulated by action potentials carried by T-tubules from innervating nerves. The dihydropyridine receptors are physically connected to ryanodine receptors on the sarcoplasmic reticulum. When the dihydropyridine receptors are stimulated, they change shape, causing ryanodine receptors to open, allowing Ca2+ to flow from the sarcoplasmic reticulum into the sarcoplasm. The ions bind to the C subunits of troponin, causing them to change shape. This allows F-actin to bind to the myosin heads. Myosin are thick filaments (each myosin protein has two heads and one tail)

If I give you an illustration of sarcomere, can you label and explain the following terms: sarcolemma, sarcoplasm, sarcoplasmic reticulum, T-tubule, dihydropyridine receptor, ryanodine receptor, myosin, myosin head, myosin tail, actin, tropomyosin, troponin, troponin subunit, troponin I subunit, troponin C subunit?

Higher concentration of K+ inside the cell and higher concentration of Na+ outside the cell. This is mediated by ion channels

If changes to membrane potential requires Na+ influx and K+ efflux, how does the concentration gradient of Na+ and K+ get established?

The net flux of water is the same and it is moving across the membrane at equal rates from both sides

If the cell is not changing shape, is there a net flux of water? Is water still moving across the membrane?

K+ would flow out of the cell because its concentration is much higher in the cell than outside the cell

If the cell membrane was made more permeable to K+ (opening of K+ channels) would K+ flow into the cell or out of the cell?

Changing membrane permeability

If the membrane potential is -70mV, how is K+ efflux possible?

Action potentials always move from the axon hillock towards the axon terminal.

In what direction does action potentials travel on a motor neuron?

Lymph and transcellular fluid

List some minor extracellular fluids.

neurons, cardiomyocytes, myocytes

List three cells that can undergo changes to membrane potential.

Increase the concentration of Molecule A in the ECF to increase rate of diffusion; lower concentration of Molecule A in the ECF to decrease the rate of diffusion

Molecule A cross a cell membrane via simple diffusion. How can you increase the rate of diffusion for molecule A? How would you decrease the rate?

plasma, interstitial fluid, plasma, lymph, transcellular fluid

Name some extracellular fluid.

Important neurotransmitter in PNS; released from sympathetic nerves that supply smooth muscle, cardiac muscle, and exocrine glands; also acts in CNS in pathways involved with memory, mood, emotions, behavior, sensory perception, sleep, and muscle movements

Norepinephrine

Acts in CNS in pathways involving mood, emotions, behavior, appetite, states of consciousness, and muscle movements

Serotonin

Over-consumption of water dilutes electrolytes in the blood, cells become hypertonic to their surroundings, leading to lysis. Sports drinks have more solutes, and are thus isotonic relative to the cells and isosmotic to the blood.

There has been incidences of death during water drinking contests. How is water toxicity possible? Sports drinks are more osmotically balanced than water. Would consumption of sport drinks in place of water (assuming equal volume) be safer for the contestants?

Neurons may receive input from multiple sources, and one neuron can synapse with multiple neurons.

Think about the idea of convergence and divergence. Consider how this concept complicates understanding of the brain.

EPSP: the change in membrane voltage of a postsynaptic cell following the influx of positively charged ions into a cell (induce depolarization) IPSP: an inhibitory synaptic potential that makes a postsynaptic neuron less likely to generate an action potential (induce hyperpolarization)

What are excitatory (EPSP) and inhibitory (IPSP) postsynaptic potentials?

concentration gradient of substance, distance (thickness of membrane), surface area of membrane, lipid solubility, molecular weight of substance

What are five factors that influence the rate of net diffusion across a cell membrane?

lipid-rich insulating substance surrounding the axons of many neurons, allowing for faster transmission of electrical signals

What are myelin sheaths?

A gap in the myelin sheath of a nerve, between adjacent glial cells.

What are nodes of Ranvier?

1. Size of muscle fiber - there are greater amounts of actin and myosin, this means more cross bridges can form and thus a stronger contraction. (increased force) 2. Number of active muscle fibers (increased force) 3. Frequency of stimulation force-frequency relationship: The muscle contracts after one stimulation and relaxes. If frequency stimulation is increase, muscle may not properly relax and more Ca2+ accumulates. Thus, more contraction (increased force) 4. Length of sarcomere length-tension relationship: The more heads pull the actin, the stronger the contraction. Isotonic contraction (increase in length, but no change in tension) is when there is perfect actin-myosin overlap. In the case of the biceps brachii, when contracted, there is some overlap between actin filaments, weakening the contraction. When the muscle is straightened, actin filaments slide away from the M line, decreasing actin myosin overlap. 5. Velocity of muscle shortening: the quicker the muscle shortens, the faster the actin filament is pulled towards to center of the sarcomere. However, if the actin moves too fast, then fewer myosin heads can bind. Thus, less cross bridge formation. (lowering velocity increases force)

What are the five factors affecting the force of contraction? How each of these factors affects contractile force?

Dendrites, cell body, axon, axon terminal

What are the major parts of the motor neuron?

Concentration gradient of both ions and the cell being permeable to each ion

What are the two factors that drive the flux of K+ and Na+ across the membrane?

intracellular fluid and extracellular fluid

What are the two major categories of body fluids?

Na+ and Cl-

What are the two major ions in the ECF?

K+ and PO43-

What are the two major ions in the ICF?

Interstitial fluid and plasma

What are the two major types of extracellular fluid?

Absolute refractory period: a second action potential cannot occur because the Na+ channels are already open and cannot open any more to increase Na+ flux, or they are closed and cannot yet open. Relative refractory period: a second action potential can be stimulated but it would require a very strong stimuli to overcome the membrane potential to open the Na+ channels. This is important for situations where a very high frequency of action potentials is necessary (membrane potential may not return to resting potentials until the stimulus has ceased).

What are the two refractory periods?

At the axon terminal (presynaptic cell) the action potential activates voltage-gated Ca2+ channels. This causes an influx of Ca2+ which then initiates the release of neurotransmitters. In this example, the neurotransmitters are housed in vesicles called synaptic vesicles., the influx of Ca2+ causes exocytosis and the neurotransmitter is released into the synaptic cleft.

What causes neurotransmitter to be released?

cardiac muscle cells

What cell has muscarinic receptors?

skeletal muscle cells

What cell has nicotinic receptors?

K+ channel

What channel is open during repolarization?

Na+ channel

What channel is open to allow depolarization to threshold?

K+ channel

What channel opens upon reaching threshold potential?

The action potentials trigger the release of neurotransmitters into the synaptic cleft

What do action potentials do once they reach the axon terminal?

The action potentials propagate along the axon (particularly at the nodes of Ranvier in myelinated axons)

What happens to the action potential generated at the axon hillock?

The charge of the cell becomes more negative as K+ flows out of the cell.

What happens to the charge of the cell when the cell membrane is more permeable to K+?

The cell becomes more positive as Na+ moves into the cell.

What happens to the charge of the cell when the cell membrane is more permeable to Na+?

The neurotransmitter diffuses across the synaptic cleft to activate receptors on the postsynaptic cell. The activation of the postsynaptic receptor will increase membrane permeability to specific ions resulting in a change in membrane potential of the postsynaptic cell

What happens to the neurotransmitter after it is released?

Graded potentials are changes in membrane potential that very in size, as opposed to being all-or-none; depends on strength of stimuli

What is a graded potential?

Contiguous conduction is continuous, where one action potential triggers the next and so on, along the axon, every portion of the membrane undergoes action potential (take each stair in stair case)

What is contiguous conduction?

One characteristic of graded potential is that the change in membrane potential diminishes it travels away from the site of activation

What is decremental spread?

Intracellular fluid is found within our cells.

What is intracellular fluid? Where is if found?

Depolarization to threshold can also occur if two cells fire close enough that the depolarization can be summed. Such cases with input from two different presynaptic cells is referred to as spatial summation.

What is spatial summation?

Phospholipids, cholesterol, proteins (sometimes glycosylated), and glycolipids

What is the basic composition of the cell membrane?

Maintain durability and fluidity

What is the function of cholesterol in the cell membrane?

Create a barrier between the ECF and the ICF

What is the function of the cell membrane?

The difference in electric potential between the interior of the cell near the membrane and the exterior of the cell near the membrane.

What is the membrane potential? Be descriptive.

When neurotransmitters interact with receptor proteins on the membrane of the postsynaptic cell, ionic channels on the membrane either open or close. When these channels open, depolarization occurs, resulting in the initiation of another action potential.

What is the outcome on the post-synaptic cells after neurotransmitter release?

These are the two ions involved in generating action potentials

What is the significance of Na+ and K+ flux?

The action potential occurs at the axon hillock and moves down the axon to the axon terminal

What is the significance of the axon hillock?

Na+ and K+

What is the significance of the difference in ion composition across the cell membrane?

The maximum rate of transport during facilitated diffusion

What is the transport maximum?

The threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. At this threshold, both Na+ and K+ channels open (Na+ is slightly faster)

What is threshold potential? What occurs when threshold potential is reached?

the effect a solution has on cell volume

What is tonicity?

Carriers/channels (transport of molecules) and receptors

What purposes may protein embedded in the membrane serve?

cellular communication with environment and transport of molecules across membrane

What purposes may protein near the cell serve?

nicotinic and muscarinic receptors

What receptors can bind ACh?

Dendrites

Where are incoming signals received by the motor neuron?

Intracellular fluid (ICF)

Where is most of the fluids in our body located?

Graded potentials are generated by the dendrites or cell body and propagate towards the axon hillock.

Where on a neuron does graded potentials occur?

pre-synaptic neurons

Which cell releases neurotransmitters?

Neurons with myelinated axons

Which cells support saltatory conduction?

ICF

Which fluid compartment has the highest concentration of K+?

ECF

Which fluid compartment has the highest concentration of Na+?

Carrier-mediated transport

Which modes of molecule movement across the cell membrane has a transport maximum?

Action potentials only move towards the axon terminal because of the refractory period.

Why are action potentials always forward moving?

The change in potential is not sufficient to reach the threshold

Why does firing of excitatory cell 1 (Ex1) one time not trigger an action potential (AP)?

The cell membrane is destroyed and all intracellular components (e.g. organelles) are released into the environment, so cell loses function

Why does rupture of the cell membrane cause cell death?

Extracellular fluid

You are extracting five teeth from a patient as part of a periodontal treatment plan. The patient is taking warfarin. Midway through the extractions, the patient starts bleeding profusely and is losing a significant amount of blood. Which fluid compartment will lose the largest percentage of it's volume?