Lecture 30. Neuromuscular section 1,2,3,5,6 (Strauch)

Which of the following is least important for the development or maintenance of a resting membrane potential? A. Na-K ATPase membrane pump B. Non-permeable fixed anions C. A diffusion gradient for potassium from inside to outside D. A high resting permeability for potassium in the membrane E. A high extracellular concentraction of sodium

E. A high extracellular concentraction of sodium

The velocity of shortening is inversely related to _________ generated by the imposed _________.

Force Load

Explain impulse transmission at NMJ. What are some mechanisms whereby normal transmission may be disrupted? -Impulse conduction at the NMJ consists of the following steps and following mechanisms for interfering w/ transmission: 1. ACh __________ from acetyl CoA and choline by ________ acetyltransferase. No important blockers for this step 2. ___________ of ACh in synaptic __________. Certain _________ poisons release ACh (loss of stored ACh) 3. ____________ of ACh. _____________, due to insufficient amounts of extracellular Ca2+, results in diminished ACh ___________ and weakness or paralysis of the muscle. _____________ toxin prevents vesicle fusion directly resulting in muscle paralysis 4. ACh combining with post-synaptic _________ receptor triggering the __________ of cation channels and depolarization of the _____-_______. Competitive blockers of the ___________ receptor (curare) prevent ACh from occupying the _________ and therefore cause muscle relaxation and paralysis. Also, auto-immune diseases such as ___________ __________ can destroy ____________ causing paralysis 5. _____________ of released ACh by acetylcholinesterase. ____________ of acetylcholinesterase prevent _________ of ACh and can enhance transmission if compromised or can produce a depolarizing _____________ and paralysis

1.Synthesized Choline 2.Storage Vesicles Spider 3.Release Hypocalcemia Botulinum 4. Nicotinic Opening End-plate Nicotinic Receptor Myasthenia gravis Receptors 5. Termination Inhibitors Removal Blockade

Therefore, the following four factors describe the genesis of the membrane potential: 1. The _____________________ gradient for potassium from ____________ to ____________ the cell 2. The high _________________ of potassium in the resting membrane 3. The fixed ___________ charges within the cell 4. The _____________-_______________ ATPase pump

Concentration Inside Outside Permeability Anionic Sodium-potassium

As ATP is split, the ____ which is formed is rapidly ____________________ to ATP by the transfer of a high-energy ___________ from creatine phosphate. The total amount of enery available from creatinine phosphate is also limited, requiring replenishment from ___________ and oxidative _________________. When ___________ is plentiful and able to keep pace with energy demands, maximum energy is produced through _________ glycolysis. If oxygen supply is insufficient, ___________ is not carried through the _______ acid cycle but rather the glucose converted to _________ acid is reduced to _________ acid and an oxygen debt is created

ADP Re-phosphorylated Phosphate Glycolysus Phosphorylation Oxygen Aerobic Glucose Citric Pyruvic Lactic

The energy for cross-bridge formation comes directly from the splitting of ______. Energy required for ion pumping is also from _____. The amount of energy stored as ATP is extremely small, being able to sustain maximal contraction of a muscle for only a few ____________.

ATP ATP Seconds

The specific features of neurotransmission at the NMJ can be described. The neurotransmitter substance at this site is ____________________. Acetylcholine is synthesized within the prejunctional terminal from _________ ____ and __________ by the enzyme choline acetyltransferase. This enzyme is produced in the cell body and is transported down the ________ to the terminal by _____________ transport. Once synthesized, ACh is stored in ___________. When an impulse originating in the CNS reaches the nerve terminal, the prejunctional membrane is rapidly ________________ by sodium influx. Calcium is in low concentration in the extracellular fluid, but has high concentration gradient directed inward. When depolarization occurs, voltage-gated __________ channels open and calcium enters the cytoplasm. This influx of calcium causes the vesicles containing ____ to fuse to the inner terminal membrane and ___________ their contents into the cleft (_____________). Each vesicle contains many ACh molecules and the emptying of each vesicle releases a quanta of ACh. In response to an impulse, many vesicles fuse, releasing several hundred ________.

Acetylcholine Acetyl CoA Choline Axon Axoplasmic Vesicles Depolarized Calcium ACh Release Exocytosis Quanta

Just as quickly as binding and channel activation, the release of ACh takes place and the molecule is free to interact again with a receptor or have its action terminated by the enzyme __________________________. -AChE is abundant in the ______-_________ area and acts quickly and continuously to _____________ ACh to acetic acid and choline, with much of this choline being conserved by being actively taken ________ into the prejunctional terminal. This entire sequence of events takes place in a few milliseconds and the system recovers, ready to transit another ____________.

Aceylcholineasterase End-plate Hydrolyzes back Impulse

The regulatory proteins, troponin and tropomyosin, are associated with ________ and respond to changes in intracellular ___________ concentration by uncovering the active sites of actin where ________-_________ attachments with myosin are formed. -The cross-bridges, on the heads of each myosin molecule, contain _________ which hydrolyzes ATP. The released energy causes the movement of the cross-bridge, ________ the actin molecule along the myosin molecule and shortening the _____________ and thus the muscle. Relaxation occurs when calcium is taken back up into the sequestered SR.

Actin Calcium Cross-bridge ATPase Sliding Sarcomere

What is the basis for the length-tension relationship in muscle? -The length-tension relationship is the amount of ________ and _________ overlap due to stretching of the muscle. As the length of the muscle increases, the overlap of actin and myosin ______________ allowing for a greater number of _______-_________ interactions to occur and a greater development of ________ or tension. When overlap is optimal, the greatest ____________ is generated. At greater or lesser muscle lengths, the tension is proportionally less, due to less than optimal _________

Actin Myosin Increases Cross-bridge Force Tension Overlap

Explain the process of membrane excitation. How are the terms stimulus, threshold, and excitability related? What is a local response? -Membrane excitation is the process leading to the _________________ of the membrane which then results in an all or none _________ potential. Any depolarizing stimulus causes voltage-gated ____ channels to begin opening and, if of sufficient strength (____________), then the regenerative, positive feedback cycle carries the __________________ to completion at or above zero potential. -The stimulus is an energy form capable of ____________________ the membrane and when it activates the membrane to fire an action potential, then it is at least _____________ strength and if it fails to activate the membrane and causes only a _______ response which is a non-propagated, _________ depolarization, then it is sub-threshold. -_______________ is the value of the membrane voltage where activation takes place. __________________ is the voltage difference between the resting potential and the threshold value. If the threshold value becomes less negative (further from ____________ potential) then we say that threshold has increased and excitability has _______________.

Activation Action Na Threshold Depolarization Depolarizing Threshold Local Graded Threshold Excitability resting Decreased

The threshold level can be assigned as a numerical value that is the voltage at which ________________ takes place. The absolute value difference between this voltage and the voltage of the __________ potential is a measure of excitability. -The greater the voltage difference between the threshold and _____________ potential, the less excitable the tissue since a __________ stimulus would be required to reach this level. Therefore, as threshold increases, excitability ______________ and vice-versa.

Activation Resting Resting Larger Decreases

Explain "all or none" -When an action potential occurs, it follows the same _____________-______________-_______________ cycle the same way every time allowing the same amount of Na to enter carrying the same amount of _____________________. The spike looks the same and it goes to completion each time. If anything changes which can alter the rate or amount of ____ entering, then depolarization changes and the spike changes causing conduction ____________ to change. Thus, anything causing Na conductance to change (e.g., local anesthetics) or Na concentration ratio to change (e.g. hypernatremia) will change depolarization creating a new all or none condition

Activation-inactivation-reactivation Depolarization Na Velocity

In any condition resulting in decreased extracellular potassium: A. the rate of rapid depolarization of the action potential will decrease B. Excitability decreases C. Conduction velocity will decrease D. The resting membrane potential decreases E. All of the above

B. Excitability decreases

As the length of a muscle is increased, the tension it generates when contracted increases up to a maximum. Beyond this maximum, tension decreases because: A. The elastic elements in the muscle are over-stretched B. The amount of actin-myosin overlap is diminished C. Passive tension falls to zero D. The sarcoplasmic reticulum is pulled away from the T-tubule E. All of the above

B. The amount of actin-myosin overlap is diminished

Which of the following conditions produces the greatest decrease in membrane excitability? A. Hyperkalemia and hypocalcemia B. Hypokalemia and hypocalcemia C. Hypokalemia and hypercalcemia D. Hyperkalemia and hypercalcemia

C. Hypokalemia and hypercalcemia

In excitation-contraction coupling, the sites where Ca2+ binds to initiate contraction is located on: A. Actin B. Myosin C. Troponin D. Tropomyosin E. Sarcoplasmic reticulum

C. Troponin

Steps in relaxation: 1. ____ pumped back into the ____________ ____________ 2. Release of ____ from troponin 3. Detachment of _______ and _________ cross-bridges

Ca Sarcoplasmic reticulum Ca Actin Myosin

Both excitation-secretion coupling and excitation-contraction coupling are __________ mediated processes

Calcium

(Continuation) For a given temperature and ion, the equilibrium potential is totally dependent on the ________________ gradient of the permeable ion. -As you can see, a potential within the range of the membrane potential has developed because: 1. Ten fold concentration gradient for ____ 2. Its ________________ and therefore diffusion or conductance from side A to side B without Cl- If the membrane is permeable to Cl- rather than K+, you should be able to predict the result. We will observe the development of a voltage with the meter eventually pointing to a _______________ value of approximately +60mV. This diffusion potential model can be extended to explain the cell membrane potential with slight additions and modifications. In excitable cells, such as mammalian skeletal muscle (-90mV), the major ions in the beaker are: - ________ intracellular K+ compared to extracellular -___________ intracellular Na+ compared to extracellular -____________ intracellular Cl- compared to extracellular - fixed intracellular anions

Concentration K+ Permeability Positive High Lower Lower

Explain membrane refractoriness. How is it measured and why is it important to the normal function of excitable cells? -Membrane refractoriness is the result of the voltage dependent _________ in Na channel _____________. -When absolutely refractory, not enough channels have ____________ to allow a second depolarization to take place regardless, the strength of the stimulus. -When relatively refractory, enough channels have _______________ to allow a greater than threshold stimulus to cause a second depolarization. When all channels have reactivated and the membrane is no longer _______________, a threshold stimulus will elicit a second, __________ looking response -The period of absolute plus relative refractoriness is the total refractory period. -The importance of refractoriness is that it controls firing ______________ of a tissue. If a threshold or normal stimulus is causing excitation, then the tissue can only fire at the end of the total ______________ period. Any pertubation which changes the time required for ___________________ to occur will change the time required for membrane reactivation and thus refractoriness.

Delay Reactivation Reactivated Reactivated Refractory Normal Frequency Refractory Repolarization

When a stimulus of sufficient strength causes the membrane to _____________ to the threshold level, a sudden change in the electrical characteristics of the membrane take place. As soon as the voltage inside starts to become less ___________ (____________), some voltage-gated ___________ channels begin to ___________ or open

Depolarize Negative Depolarize Sodium Activate

When a length-tension curve is generated, the muscle is passively stretched causing _________ elements in the muscle to be stretched and sarcomere length to ___________. -The force developed by stretching only is called ___________ tension. -The tension developed each time the muscle is stimulated to contract a new length is the _______ tension. -The difference between passive tension and total tension is the _______ tension which results from cross-bridge formation and sarcomere shortening. An important example of the regulatory role of the length-tension relationship is seen in ventricular filling in the heart which stretches the cardiac muscle, resulting in increased contractile _______ and pumping pressure up to a point, beyond which excessive stretch leads to _____________ contractile force and cardiac failure

Elastic Increase Passive Total Active Force Decreased

What specifically can you determine from the Nernst and Goldman equations? -The Nernst equation provides a numerical value of the ________________ potential, which is the voltage developed when the diffusible ion produces a __________________ of charges across a membrane. At this potential, the system is in ________________ and diffusion down a concentration gradient is ______________ by diffusion in the opposite direction down an ______________ gradient, hence no net diffusion. The value of the Nernst equation is dependent on the valence of the ion, the temperature and the ________________ ratio inside/outside of the ion. -The Goldman equation is a steady-state equation which provides a steady-state potential for two or more ions with different concentration ratios and different ___________________. It more accurately describes the membrane potential than does the equilibrium potential for a single ion

Equilibrium Separation Equilibrium Balanced chemical Concentration Permeabilities

_______________ membranes are capable of initiating and/or conducting and electrical signal or ____________. This signal contains information whch causes a tissue or organ to initiate a _____________ such as contraction of a muscle or a secretion from a gland. In the CNS, information is integrated to trigger a response or modify a body function. Some tissues, including heart and smooth muscle, are ___________________ active yet nerve signals modify the state of activity.

Excitable Impulse Response Spontaneously

Muscle __________ closely parallels depletion of muscle glycogen when energy demand exceeds energy _________. A period of recovery is required to metabolize ______ acid and replenish creatine phosphate and ATP stores. Muscle fibers of the _____ type contain the oxygen storing protein _____________, a rich blood supply and plentiful mitochondria adapting them for aerobic metabolism and activity requiring endurance. ______ fiber types, on the other hand contain __________ and enzymes necessary for rapid, ____________ metabolism. They are adapted for fast, powerful contractions, but fatigue readily

Fatigue Supply Lactic Red Myoglobin White Glycogen Anaerobic

Each muscle is comprised of many multi-nucleated cells or ________. Each muscle fiber in turn is made up of _____________ containing numerous _____________ attached end to end. The sarcomere contains _______________ of thick _________ surrounded by thin ________ in a hexagonal array. -Each actin filament is attached to the __-______, producing the light area termed the __-_______. -The myosin filaments are attached to the __-______, producing the ___-__________ of thick filaments -___-________ is the darker area where actin and myosin overlap

Fibers Myofibrils Sarcomeres Myofilaments Myosin Actin Z-disc I-band M-line H-band A-band

Since information, such as that carried by nerves, is coded by _______________, it is imperative that the impulse remains invariant in amplitude and duration. Otherwise, large impulses would contain a ____________ signal or amount of information than small impulses. This would severely comprimise the ability to integrate information and to function normally. As an example, when skeletal muslce is stimulated to contract by a single impulse, it responds essentially with the same twitch ________ every time. To increase the strength of contraction, the signal does not become _________, but the frequency of impulses becomes ___________. At high frequencies, each innervated fiber responds with ____________ contraction. Muscle can also change contractile force by recruiting more _________ to contract by bringing additional impulses via _______ motor nerve fibers. As long as no disease processes, chemical influences, or damage alter a normal ____________ tissue, the impulses which travel over its membrane surfaces do not vary in ______, conduction velocity, or physical properties. Integration of signals does occur at _______________ between cells (nerve synapses) and at the transducers which respond to different forms of stimuli, the sensory receptors.

Frequency Different Force Larger Greater Maximal Fibers More Excitable Size Junctions

The ration of nerve:fiber varies considerably depending on muscle _____________. As the demand for greater force of contraction is required of the muscle, ________ individual motor units containing _______ fibers per unit are made to contract. As individual motor units contract, they do so __________________ such that contraction becomes smooth and sustained if necessary. Also, as the frequency of firing of motor units is increased, the time between individual, discrete twitches is _______________ to a point where relaxation of the previous twitch becomes _______________ and the next contraction builds upon the previous one. This ________________ produces a smoother, more forceful contraction. When the frequency becomes so fast that no _______________ occurs between contractions, then contractions become fused, producing _____________

Function More More Asynchronously Shortened Incomplete Summation Relaxation Tetanization

Since depolarization and repolarization involve both a driving force (____________) and a permeability (___________________) change for sodium and potassium, anything which alters either the _______________ gradient or permeability to these ions is likely to alter the action potential configuration and the properties of impulse conduction. Conditions of increased extracellular sodium (______________) or decreased extracellular sodium (________________) are reflected in changes in rate of ____________________ and the amplitude of depolarization. Because the velocity of impulse conduction is directly dependent on rapid phase of __________________, conditions resulting in sodium imblance can alter impulse _______________. Many chemical agents alter sodium conductance such that then block sodium ____________. Toxic substances such as tetrodotoxin +TTX and certain venoms block irreversibly. Useful drugs, including local __________________ and CNS drugs block __________ channels, but do so reversibly

Gradient Conductance Concentration Hypernatremia Hyponatremia Depolarization Depolarization Conduction Channels Anesthetics Sodium

If the normal concentration of extracellular potassium is 4mM and the outside to inside ratio is 4/155 the calculated equilibrium is -97mV. When the concentration of potassium bathing the cell is experimentally halved to 2mM or doubled to 8mM, the corresponding membrane potential shifts to a ____________ or _____________ potential respectively. This is the primary evidence for ______________'s major role in the membrane potential of most animal cells. This means that potassium is quite ______________ when the membrane is in a __________ or inactive state and is the _________ contributor to the measured potential. Chloride also happens to be fairly ____________, but is passively distributed according to the potential established when _______________ diffuses outward creating a net negative charge from the fixed _________ such as phosphate and carboxyl. Chloride does not diffuse ___ because of this repelling _______________ voltage and aligns itself according to the potential created by potassium diffusing out. Chloride also maintains the electroneutrality for ___________ outside

Higher Lower Potassium Permeable Resting Major Permeable Potassium Anions In Negative Sodium

What is the basis for the resting membrane potential in excitable cells? A. The membrane has a high resting ______________ to K+ B. K+ has a concentration gradient Kinside ___ Koutside C. Fixed, non-diffusible _______ charges inside D. The ____________-___________ pump to maintain the concentration gradients

Permeability > Anionic Sodium-potassium

Certain conditions can change the threshold level, such as the loss or addition of calcium to the extracellular fluid. Calcium interacts with the membrane as a membrane stabilizer so that during conditions of reduced serum calcium, ________________, the membrane becomes destabilized, threshold is ______________ and excitability ________________. An increased calcium level, ______________, results in opposite changes. When extracellular calcium is high this results in a(n) ______________ in threshold and excitability is _________________. Another important factor which can alter excitability is the level of the resting potential. If threshold remains unchanged yet the resting membrane potential decreases (becomes less ___________), then the voltage difference between the resting potential and the threshold is _______ and the tissue has become more ______________. The condition of ______________ (elevated extracellular potassium) _________ the resting potential by decreasing the gradient for potassium to diffuse out of the cell and thus increases _____________. _________________, reduced extracellular potassium, produces the opposite effect, i.e., an increased resting potential and a decrease in ______________.

Hypocalcemia Decreased Increases Increase Decreased Negative less Excitable Hyperkalemia Lowers Excitability Hypokalemia Excitability

The NMJ transmittion, with its many steps and individual processes, is subject to considerable alteration, by disease, drugs, and toxins Important examples include: 1. ____________________ paralysis in which insufficient calcium is avaliable to trigger adequate ______ release 2. Prevention of ACh release and paralysis by irreversible binding of _______________ and other toxins 3. Massive release of ACh resulting in depletion of stored ACh and paralysis by _________ ___________ _____________ venom 4. Blockade of the nicotinic receptor resulting in paralysis by neuromuscular blocking drugs such as _________ 5. _____________ of acetylcholinesterase, allowing accumulation of ACh which may facilitate transmission when weak or may block transmission by continual depolarization of the end-plate, resulting in paralysis 6. Destruction of nicotinic receptors by the auto-immune disease __________________ __________, producing muscle weakness due to inadequate transmission

Hypocalcemic ACh Botulinum Black Widow Spider Curare Inhibition Myasthenia gravis

Steps in excitation-contraction coupling are as follows: 1. Transmission of ___________ from motor nerve to muscle 2. Propagation of action potential over sarcolemma and into ___-_________ 3. Depolarization of sarcoplasmic reticulum at triad by action potential causing release of ____ 4. Binding of Ca2+ to __________ causingg tropomyosin to uncover active sites on ________ 5. Formation of _______-________ between actin and myosin 6. Cleavage of _____ and release of energy with the ___________ of actin along myosin and development of tension and muscle ______________ 7. Pumping of _____ back into SR and removal of Ca2+ from ____________ 8. Covering active sites on _________ by tropomyosin and relaxation

Impulse T-tubules Ca2+ Troponin Actin Cross-bridges ATP Sliding Shortening Ca2+ Troponin Actin

Several things occur immediately to oppose the sudden _________ of sodium. First, sodium channel activation is ______-lived, and channels begin to actively close (inactivate) after a few tenths of a millisecond. Also, before the action potential begins, both the concentration gradient and electrical gradient for sodium are oriented _________. As the inside of the cell briefly becomes positive (due to ___________ influx), the electrical gradient is abolished during this period of reversed polarity. The second major event of the action potential is __________________. At the same time the depolarization starts to open ___________ channels, it also starts opening _______________ channels. This ______________ efflux also tends to oppose sodium channel activation, especially during subthreshold depolarizations. These voltage gated K+ channels open ________ and __________, allowing potassium to _________ the cell at a much lower rate than sodium __________ but for a much longer period of time. Not only are potassium channels opening but as sodium enters carrying a ________________ current, the inside transiently becomes positive, abolishing the inward ____________ gradient that opposes the efflux of potassium down its concentration gradient at equilibrium. The outward movement of _______________ carrying positive charges restores the membrane potential to its original ___________ resting value and in doing so brings about sodium channel _______________, which is also ___________ dependent. If partial depolarization or incomplete repolarization occurs, the sodium channel _____________ is impaired. Potassium efflux is not a positive feedback process, but rather restorative (___________ feedback)

Influx Short Inward Sodium Repolarization Sodium Potassium Potassium Later Slower leave Enters Depolarizing Electrical Potassium Negative Reactivation Voltage Reactivation Negative

What are the two major differences regarding the membrane potential between excitable and non-excitable cells? -The _________________ of the membrane potential in excitable cells is much greater than non-excitable cells -The membrane potential can be quickly but briefly ______________ in excitable cells due to the active participation of the membrane to cause ion channels to _________ during an action potential

Magnitude Reversed Open

Excitable cells differ from non-excitable cells in that the magnitude of the _______________ potential is _____________ in excitable cells and that the membrane of excitable cells can be activated to temporarily undergo changes which allow an __________ to be conducted. The membrane potential of excitable cells is referred to as a ________________ ________________ potential to distinguish this condition from an __________ potential during which the membrane actively responds with a conducted impulse (usually resulting in some action). An ___________ is the signal or transfer of information throughout the animal's body and is reflected in the membrane change as an action potential. The resting membrane potential is also a ___________-____________ potential, which means that even during the inactive or resting condition, ions are constantly "___________" down their concentration gradients tending to cause the membrane's "battery" to run down with the voltage going toward zero. Under normal conditions, this does not occur because the membrane pump is always in the background maintaining these ionic ______________.

Membrane Greater Impulse Resting membrane Action Impulse Steady-state Leaking Gradients

All living cells have a _______________ ______________, which means that a voltage (potential) exists between the inside and the outside of the cell, across the _______ _____________. This _____________ develops because there is a separation of charges across the cell membrane with a relative excess of positive charges (__________, which are attracted to a negative electrode or ___________) or negative charges (________, which are attracted to a positive electrode or _________) on one side versus the other. In most cells, this potential is small, in the range of 5-20mV. In cells which are excitable, such as nerve and muscle, the magnitude of this potential is much ______________, ranging from 50mV to more than 100mV. We assign a negative value to the _____________ of the cell with respect to the outside. It is possible to measure the potential by several different techniques. The most common method is to employ a __________________ which is a very small, electrolyte filled open-tipped glass electrode which penetrates the interior of the cell causing minimal ____________ yet allowing the voltage across the cell membrane to be accurately determined. The large membrane potential in _________ cells provides the energy or power which is necessary to allow the conduction of a message or ___________ along the surface of nerves and muscles.

Membrane potential Cell membrane Potential Cation Cathode Anions Anode Greater Interior Microelectrode Damage Excitable Impulse

Explain a muscle contraction on the basis of the firing of motor units -When a muscle contracts, it is the result of many _______ ________ firing _______________. This has a dampening effect that results in a ___________ contraction. As individual motor units fire more frequently and a second contraction takes place before the first one is ____________, then ______________ or adding of force occurs resulting in a smoother, more ______________ contraction. When frequency of firing causes complete fusion of contraction, the contraction is _______________. As the demand for greater force of contraction is made, then the number of motor units which are firing _____________

Motor units Asynchronously Smooth Complete Summation Forceful Tetanizing Increases

Excitation-contraction coupling is the process whereby an action potential at the surface of the __________ cell (fiber) initiates the process of _____________. -____________ muscle (skeletal and cardiac) contracts rapidly and has developed specialized subcellular structures and organelles for this purpose

Muscle Contraction Striated

Explain energy utilization in muscle -ATP is the ultimate source of energy for ________ contraction. Energy for the formation of ATP is stored as ___________ phosphate. With normal activity the energy supply is maintained by ___________ glycolysis. During periods of excessive muscular activity, ____________ glycolysis occurs with the production of __________ acid. In periods of anaerobic activity, an ________ debt is created, During recovery when oxygen availability exceeds demand, lactic acid is metabolized and __________ stores are replenished

Muscle Creatine Aerobic Anaerobic Lactic Oxygen Energy

(Continuation from previous card) Potassium, because of its permeability in the membrane, has a ______ diffusion across the membrane from its ______ concentration on side A toward the low concentration on side B. As K+ diffuses down its _________________ gradient, Cl- remains behind due to its lack of ________________ through this membrane. This results in a net accumulation of ___________ charges building up on side A of the membrane (net excess of Cl-) and a net accumulation of ______________ charges on side B (net excess of K+). Now we have not only a concentration gradient for K from side A _________ toward side B, but we also have an ____________ gradient in the opposite direction from _____________ on side B toward ____________ on side A. This charge separation involves relatively few ions across a very short distance. Net diffusion of K+ continues until an ________________ is reached at which time the tendency for K+ to diffuse down its concentration gradient is exactly ________________ by its tendency to diffuse down its electrical gradient back toward side ___. -At this equilibrium no net diffusion is taking place and the voltage at which this occurs is called the ________________ ________________. This is described by the __________ equation

Net High Concentration Permeability Negative Positive Downhill Electrical Positive Negative Equilibrium Balanced A Equilibrium potential Nernst

If we first separate two sides of a beaker by a nonpermeable (insulating) membrane and we place on side A a 0.1 molar solution of KCl and we place on side B a 0.01 molar solution of KCl, using an electrical measuring device, we can determine that ___ voltage or potential ______________ exists between side A and side B. Now, if we impose a selectively permeable (________________) membrane with the characteristic of only being permeable to the cation (potassium) and we separate the beaker into two compartments with this cation selective membrane, we have produced the conditions for a ___________ cell. We will observe the development of a voltage with the meter eventually pointing to a ___________ value of approximately -61mV (potassium getting diffused down its concentration gradient)

No Difference Semipermeable Diffusion Negative

Because activation of the membrane depends on a voltage shift and because reactivation of the membrane also depends on a return to ___________ resting levels, if hyperkalemic depolarization is severe, the membrane remains ______________, is unable to be _______________, and becomes less excitable. A condition known as _________________ occurs in which the membrane remains inexcitable due to persistent or gradual depolarization

Normal Depolarized Reactivated Accommodation

Describe the process of membrane activation regarding the voltage gated Na channels -Na channel gate activation involves the cycle of ____________ and closing of the channel to the passage of Na ions. In the resting state, the channels are _______, waiting for a depolarizing ___________ to be activated or opened. At activation, they ________ allowing Na entry, but quickly undergo _______________ and actively _______. They remain _____________ until the membrane potential repolarizes back to or close to its ___________ value. At this point the channels are again in the __________, _________ to be activated state. This voltage dependent delay in ___________________ accounts for membrane refractoriness

Opening Ready Stimulus Open Inactivation Close Inactivated Resting Resting Ready Reactivation

The measured membrane potential does not coincide exactly with the values calculated from the Nernst equation, but deviates to less negative values at low extracellular potassium values. This happens because sodium, which is not very ______________ in the resting state, does tend to leak in as the membrane potential becomes _________ (more _____________). The more negative the inside of the cell, the greater attractive force for __________, allowing more positive ions to enter the cell and reduce ___________. A relationship which more accurately describes the membrane potential is the __________ equation. This equation considers not only the concentration ratios of these three important ions, but also takes their respective ________________ into account in calculation of the equilibrium potential.

Permeable Greater Negative Sodium Potential Goldman Permeabilities

The cell membranes of excitable cells differ from other cells by being selectively _________________ to certain ions which allow them to develop a small, but significant ______________ between the interior and exterior of the cell. These membranes are also endowed with ______ channels which respond to a stimulus by ____________ and therefore allowing ions to flow _________ the membrane. This flow of ions carries a ___________ inward or outward across the membrane and associated with this flow of charge (or current) is a transient ___________ change reflected in the electrical signal or impulse

Permeable Voltage Ion Opening Across Charge Voltage

When a stimulus is applied, either physiological or from a stimulating electrode, the membrane potential is displaced from its normal level of ________________. __________, that is the flow of charges, will either add to the membrane potential, making it more negative (_____________________) or subtract from the membrane potential, making it less negative (_________________). When the current is depolarizing and if the strength of the applied stimulus is adequate to elicit an action potential, we say that _______________ has been reached and _______________ has occurred. This threshold level is different for different tissues and may change in response to changes in the __________________ of the cell or with damage to the cell. The threshold level, sometimes referred to as the _________ level, is the point at which ________________ of the membrane takes place resulting in the regenerative phases of an action potential and a conducted ___________. Stimuli which fail to elicit an action potential are _________________ and the changes in the membrane potential as a result of a subthreshold stimulus are passive in nature. Passive changes in the membrane potential are referred to as a ________ response (non-propagated) and are _________ (amplitude is proportional to stimulus size). This is in contrast to an action potential which is ____ or _______ (independent of size of the stimulus as long as it is at or above threshold, i.e, ________ threshold) and is a propagated impulse (not _________). Examples of local responses include the __________ potential at sensory receptor endings, the __________ potential occurring at nerve junctions and the ____________ potential which is the local circuit of current flow associated with the propagation of an impulse

Polarization Current Hyperpolarization Depolarization Threshold Excitation Environment Firing Activation Impulse Sub-threshold Local Graded All None Supra Local Generator Synaptic Electrotonic

As these first channels begin to open, allowing more _____________ charged sodium to rush in, the inside becomes less _____________. This regenerative cycle of sodium influx is __________ feedback in nature and if the depolarization is to threshold, activation of a sufficient number of channels will take place to carry the process to completion

Positively Negative Positive

Steps in Contraction 1. End-plate _____________ 2. Conduction of muscle ________ potential 3. Inward spread of depolarization along ___-_________ 4. Release of ____ from sarcoplasmic reticulum 5. Diffusion of ___ to troponin binding site 6. Binding of Ca to ____________ uncovering actin binding sites 7. Formation of _______-_________ between actin and myosin 8. ___________ of filaments and shortening of ___________

Potential Action T-tubules Ca Ca Troponin Cross-bridges Sliding Sarcomere

ES coupling is the term sometimes applied to the link between nerve stimulation and glandular secretion, but more commonly it refers to the mechanism of _____________ neurotransmitter release. -Neurotransmission at all chemical ____________ in animals share certain mechanistic features in common. These include presynaptic mechanisms for 1. Neurotransmitter ________________ 2. Neurotransmitter ____________ 3. Neurotransmitter ___________ 4. A post-synaptic mechanism of neurotransmitter receptor __________ transduction 5. Mechanism of neurotransmitter _______________ The description presented here deals only with the specialized synapse between a motor nerve and skeletal __________, the _____________________ junction. Anatomically, this site consists of a branched nerve terminal that is devoid of myelin, a junctional ________ and an invaginated muscle surface or _____-________

Pre-synaptic Synapses Synthesis Storage Release Signal Termination Muscle Neuromuscular Cleft End-plate

The functional unit of striated muscle is the _____________, the area lying between adjacent __-_________, that shortens upon contraction. The muscle cell membrane, the ______________, conducts the action potential along the cell surface. A system of _____________ tubules (__-tubules) invaginate the cell surface and communicate with the _______________ fluid, carrying electrical signal to the ____________ of the sarcomere. Specialized endoplasmic reticulum, the ______________ reticulum, surrounds each myofibril and controls the movement of ___________ within the muscle. Calcium is released from the ___________ __________ and is sequestered in the ________ sacs of the SR. The point of intersection, where the electrical signal (__-_______) is relayed to the site of ___________ storage (SR) is called a _________. As in all muscle, including smooth muscle, specialized proteins are present that undergo changes in intramolecular forces, producing shortening and contraction. The pattern of arrangement of these proteins within the fiber gives rise to the ______________ seen microscopically

Sarcomere Z-discs Sarcolemma Transverse T Extracellular Interior Sarcoplasmic Calcium Terminal cisternae Lateral T-tubules Calcium Triad Striations

Calcium's crucial role here provides the link for excitation-______________ coupling. Following the release, ACh rapidly diffuses across the ______ where the ____-_______ is endowed with cholinergic nicotinic receptors associated with ion channels. When ACh binds briefly to one of these _________-gated channels, the channel opens and conductance to cations increases. The depolarization of the postjunctional _____-_______, known as end-plate potential (EPP), is due primarily to sodium __________. This EPP spreads throughout the terminal and on into the ___________ as a muscle action potential, which initiates _____________.

Secretion Cleft End-plate Ligand End-plate Influx Muscle Contraction

The genesis of the membrane potential is due to: 1. _____________ __________________ of the cell membrane allowing certain ions to __________ freely while retarding the passage of other ions 2. Energy driven membrane pumps, primarily the _______________-_______________ ______ pump, which can contribute to and maintain this membrane potential. In the simplest explanation, we can describe a ____________ cell containing a selectively permeable membrane, a salt solution of which one ionic species is permeable in the membrane and the other ionic species is impermeable and a device capable of measuring the potential difference in milivolts between the two sides separated by the membrane. -When a salt (potassium chloride) is placed in a solvent, the salt is ________________ into two ions of opposite charge and each ion _________ within the solution until the concentration is uniform throughout the solution. Initially, diffusion from an area of _________ concentration is greater than in the reverse direction and we speak about a _____ diffusion (or gain of ions) down a _________________ (chemical) gradient. Eventually, after ___________________ takes place, diffusion continues due to the random movement of particles but no net diffusion is occurring. With equal distribution of oppositely charged particles throughout the solution, ___________________ is maintained and no voltage difference is detected anywhere in the solution

Selective permeability Diffuse Sodium-potassium ATP Diffusion dissolved diffuses High Net Concentration Equilibrium Electroneutrality

What is required for a diffusion potential and how does the potential develop? -A ___________________ membrane and one _______________ ion and one non-diffusible ion with opposite _________. The potential develops when the diffusible ion migrates from the area of ________ concentration to the area of ________ concentration, creating a relative excess of diffusible ions (__________) on the low concentration side and a relative deficiency of diffusible ions(charges) on the high concentration side. This separation of a small number of charges across a short distance provides the potential which then opposes ____________ diffusion

Semi-permeable Diffusible Charges High Low Charges Further

Compare an isometric contraction to an isotonic contraction -An isometric contraction occurs when no external _______________ takes place because the load imposed exceeds the force generated. Internal sarcomere shortening and stretching of elastic elements with the generation of results -An isotonic contraction occurs when external _____________ takes place because the force generated exceeds the load imposed. Internal shortening and heat production also accompany this.

Shortening Shortening

The total number of ions involved in one depolarization - repolarization cycle of an action potential is very ________ in relation to the total number of ions inside and outside the cell. Every time an impulse passes along the surface of an __________ cell, the changes in membrane conductances underlying the action potential cause a _________ gain in intracellular sodium and loss of intracellular potassium. The Na-K ATPase membrane pump, operating in the background, restores the ___________

Small Excitable Slight Gradients

If we solve the Nernst equation for the equilibrium potential for each of the permeable ions: It is obvious that ___________, at +66mV, cannot be the ion primarily responsible for the observed -90mV potential. Potassium, with a calculated equilibrium potential of -97mV, is close to but slightly greater than the measured potential. Chloride, at -90mV, would appear to be the best candidate for providing the membrane potential, but if we vary the chloride concentration outside the cell, we see no change in ______________ potential. When the concentration of ______________ outside is varied, we measure a corresponding shift in the value of the membrane potential

Sodium Membrane Potassium

The final factor in the genesis and maintenance of the membrane potential is the _____________-______________ ATPase membrane pump. This pump can carry _______________ back into the cell while removing ____________ from the cell. As will be discussed later, the loss of potassium from the cell and accumulation of ______________ for potassium within the cell occur during normal cellular activity. The pump can exchange an equal amount of sodium for potassium and therefore equal numbers of positive charges to maintain these ionic gradients and potentials. When no net charge is gained on either side, the pump is acting in an electroneutral fashion. On certain occasions, and in certain tissues, the pump can exchange ________ sodium ions for every ______ potassium ions. This results in a net loss of positive sodium ions and thus generates a ___________. This is referred to as electrogenic pumping and can contribute to the _____________ interior of the cell.

Sodium-potassium Potassium Sodium Sodium 3 2 Current Negative

The ____________ or force of contraction and the speed or __________ of contraction are regulated by several mechanisms. Muscle contraction can be classified as __________ or _________, but rarely is a contraction purely one or the other, but rather a ______________ of the two. A contraction is _____________ (same length) when the external length of the muscle does not shorten during contraction ___________ (same tension) when external shortening occurs while tension remains approximately constant

Tension Velocity Isometric Isotonic Combination Isometric Isotonic

What are the events underlying an action potential in terms of ionic conductance changes and ionic fluxes? -When a stimulus reaches ___________, ____ channel activation causes a large increase in ___ conductance and ___ rushes in down its concentration and electrical gradients ______________ the membrane. With a slight delay and a ____________ increase, the membrane conductance to ___ increases greater than its resting value and ___ leaves the cell down its concentration and down its electrical (now reversed) gradient carrying the __________________ current and restoring the membrane to its original ___________ condition. -Only about 1x10^-12 moles of Na per cm^2 of membrane are required to ________________ the membrane and like quantity of K+ is needed to ________________ the membrane. This amounts to a gain of only about 0.001% of total ions. Thus, with a single action potential, the total concentration of ions on either side of the membrane is imperceptibly altered.

Threshold Na Na Na Depolarizing Slower K+ K+ Repolarization Resting Depolarize Repolarize

Activation of the membrane takes place when ______________ is reached and involves the opening of ______ channels which reduces the membrane's ______________ to the passage of charged ions (current). We refer to this change in membrane resistance as a change in _________________ (g). As ion channels open, the membrane becomes more ________________ (resistance decreases) and conductance to ions _____________. Ion channels have the property of selectivity and undergo a pattern of ______________-_______________-_______________ (open-closed-ready to reopen). Many different types of membrane channels exist but by far the most studied and most relevant to the discussion of electrical properties are the ___________ and _____________ channels responsible for the ______________ and _______________ phases, respectively, of action potential. These channels are selective for each specific ion and are __________-gated. This means that their activation or opening is dependent on a change in the ___________ of the membrane, which occurs with a depolarizing stimulus. Voltage-gated channels differ from other types of channels with respect to how they are _____________. _________-gated channels open when a ligand (chemical) binds a receptor associated with the channel. Sodium channels go through a cycle ___________-____________-____________

Threshold ion Resistance Conductance Permeable Increases Activation-inactivation-reactivation Sodium Potassium Depolarization Repolarization Voltage Voltage Activated Ligand Activation-inactivation-reactivation

Purposeful muscle contractions rarely appear as __________, but rather as smooth, sustained, forceful contractions. This is due to several regulatory properties, including: A) _______________ firing of motor units B) ______________ of motor units C) tetany A ________ unit is the motor nerve and all the muscle fibers which it innervates

Twitch Asynchronous Summation Motor

Skeletal muscle makes up 40% or more of an animal's total body ________ and functions primarily to move one part of the body in relation to another. It also plays a major role in _________ regulation. Skeletal muscle is under direct control of the nervous system and thus is __________ as compared to heart and smooth muscle which are not and therefore ______________.

Weight Thermal Voluntary Involuntary

This rapid sodium influx explosively drives the membrane potential toward and even past _______ to some positive value (actually, sodium attempts to reach equilibrium potential of +60mV during this brief period of increased conductance). During this rapid phase of __________________, as many sodium channels open briefly, the membrane's permeability to sodium _______________ so that sodium conductance may increase 10,000x the resting value (sodium conductance becomes greater than the relatively high resting conductance for _____________)

Zero Depolarization Increases potassium

The ___________ of a muscle or the amount of stretch imposed on the muscle prior to contraction is an important factor in regulating contraction. The ___________-tension relationship is based on the amount of overlap between ________ and __________ filaments which varies with ______________ length due to stretching. The greater the degree of overlap, the greater the number of ________-__________ formed and thus ________ of contraction. The force of contraction is proportional to the number of _________-__________ per time. The velocity of shortening is related inversely to the _______ so that as the speed at which actin and myosin slide pass each other increases, the number of cross-bridges that can be formed ___________

length Length Actin Myosin Sarcomere Cross-bridges Force Cross-bridges Force Decreases

Conditions of potassium imbalance not only alter the __________ membrane potential and excitability but also interfere with the normal __________________ processes. Since repolarization brings the membrane potential back to its ___________ value and therefore reactivates __________ channels, the conditions of membrane ________________ and impulse conduction frequency are dependent on the repolarization and action potential duration. Any condition which speeds or delays repolarization willl alter the time during which the cell is _____________ (unable to respond normally to a stimulus)

resting Repolarization Resting Sodium Refractoriness Refractory

Once initiated, the action potential uses the _________ energy of the membrane potential to propagate from its origin to its destination undiminished in size and shape. An action potential may be initiated in several ways. In a _____________ receptor, a physical or chemical __________ provides energy which initiates an action potential. At a ___________ (or junction between two neurons), the release of a neurotransmitter substance across the synapse acts to stimulate the receptors on post-junctional neuron. In lab or clinical testing, an electrical stimulus can be applied to initiate an __________ potential. A cardiac pacemaker is an example of providing an electrical ______________ to control heart rhythm. When an applied stimulus results in a propagated action potential, then we refer to the stimulus as adequate and that the cell has been _________. The events leading from the application of the stimulus to the initiation of the action potential can be analyzed and the ease with which these events take place is referred to as membrane ________________.

stored Sensory Stimulus Synapse Action Stimulus Excited Excitability

When load imposed on a muscle exceeds the force developed by the muscle, ___________ is minimal and little or no movement is detected. When a muscle contracts without a load, then ____________ approaches maximum and movement occurs.

velocity velocity