Physiology - Musculoskeletal Block

Question 1

What is Ohm’s law?

Answer 1

V = IR

(voltage = current * resistance)

Question 2

What does the Nernst equation show?

Answer 2

The potential difference (the voltage) of a single ion type across a cell membrane is related to the ion type’s concentration gradient

(I.e. the voltage is determined by the concentration gradient)

Question 3

What does the Goldman (GHK) equation show?

Answer 3

Each ion’s Nernst potential contribution to the E_membrane is proportional to the membrane’s permeability for that ion

Question 4

True/False.

E_m and membrane voltage can be thought of as equivalent terms.

Answer 4

True.

Question 5

What electrolytes and/or other substances provide most of the charge found on the outside of the cell?

(I.e. what electrolytes are found in high concentrations in the extracellular fluids?)

Answer 5

Na⁺

Cl^{<span>-</span>}

Question 6

What electrolytes and/or other substances provide most of the charge found on the inside of the cell?

(I.e. what electrolytes are found in high concentrations in the intracellular fluids?)

Answer 6

K⁺

proteins

Question 7

What is the main ion pump maintaining cellular voltages?

Answer 7

The Na-K pump

Question 8

What are normal serum Na⁺ levels?

What are normal serum K⁺ levels?

Answer 8

140 mM (135 - 145 mM)

4.6 mM (3.6 - 5.5 mM)

Question 9

How are Nernst potentials generated?

Answer 9

Diffusion of ions down their concentration gradients

(e.g. K⁺ leaves the cell –> the cell becomes slightly more negative)

Question 10

What two gradients are being balanced to produce a single ion’s Nernst potential?

Answer 10

An electrical and a chemical gradient

(e.g. K⁺ flows out along its concentration gradient, leaving behind an electrical gradient which draws K⁺ into the cell)

Question 11

How much of the K⁺ inside a cell or Na⁺ outside the cell needs to move for a large change to occur in voltages?

Answer 11

An infinitesimal amount

(concentrations remain fairly constant)

Question 12

What is the Nernst equation for K⁺?

Answer 12

E_K = 60log₁₀ (K_o / K_i)

Question 13

From where does the ‘60log₁₀’ in the Nernst equation come?

(E_K = 60log₁₀ (K_o / K_i))

Answer 13

RT / ZF ln = ~60

• Gas constant * absolute temperature*
• /*
• valence * Faraday’s constant*

Question 14

_______ potentials are solved for individual ion potentials.

The __________ equation allows us to compare all these potentials on a single membrane.

Answer 14

Nernst;

Goldman (GHK)

Question 15

What is the most important factor determing E_m (membrane voltage) under physiological conditions?

Answer 15

The ratio of P_K to P_Na

(P = permeability)

Question 16

How can membrane potentials (E_m) change?

Answer 16

Change the ratio of Na⁺ to K⁺ permeability

(remember, Na and K concentrations hardly change at all –> only infinitesimal amounts move across membranes at any one time)

Question 17

All cells in the body have a __ resting potential (E_m).

This means all our cells are more influenced by __ than __.

Answer 17

-

K⁺, Na⁺

Question 18

What resting E_m would you find in an erythrocyte?

What resting E_m would you find in a neuron?

What resting E_m would you find in a cardiac myocyte?

Answer 18

• 10 mV
• 70 mV
• 90 mV

Question 19

What would the E_m (membrane potential) be if the charge outside and inside were the same?

Answer 19

0

(no potential difference = no voltage)

Question 20

When the E_m moves in a negative direction away from resting membrane potential, it is:

When the E_m moves in a positive direction towards zero and away from resting potential, it is:

When the E_m moves in a positive direction away from zero (the cell is now positive inside), it is:

Answer 20

Hyperpolarizing;

depolarizing;

a reversal of membrane potential (it has already depolarized)

Question 21

If significantly small currents pass through excitable cells, what response do they have?

Answer 21

Passive return to resting potential

(action potential threshold not met)

Question 22

If significantly large currents pass through excitable cells, what response do they have?

Answer 22

Active response / depolarization / action potential

(threshold surpassed)

Question 23

How does a stimulated neuron’s membrane potential decrease as a function of distance/time down the axon if the stimulation did not reach the action potential threshold?

And if it did reach the threshold?

Answer 23

It decays exponentially;

there is no decay whatsoever

Question 24

If you use a probe to stimulate an axon midway down its length, in which direction will the potential travel?

Answer 24

Both directions

(towards the synapse and towards the soma)

Question 25

True/False.

Action potentials allow for graded responses.

Answer 25

False.

They are all-or-none responses

Question 26

Which moves faster, an action potential or a different electronic potential (a subthreshold or hyperpolarizing stimulation)?

Answer 26

Electronic potentials

(action potentials are slower but don’t lose any potential with distance)

Question 27

The Nernst equation tells us that individual ions have their own voltage based on ___________ gradients.

The Goldman (GHK) equation tells us that the permeability and ___________ of these ions together can be used to determine the ___.

Answer 27

Concentration;

Nernst potentials,

E_m (membrane potential)

Question 28

If you increase the permeability of a membrane towards a particular ion, what will happen to the overall E_m (membrane potential)?

Answer 28

It will shift towards the Nernst potential for that ion

Question 29

All cellular membrane potentials (E_ms) can be found between the Nernst potentials for what two ions?

Answer 29

Sodium_______________________________________

0____________________________________________

Potassium_____________________________________

Question 30

What event triggers the changes in permeability to Na⁺ and K⁺ necessary for an action potential?

Answer 30

Membrane depolarization

Question 31

Upon membrane depolarization reaching threshold in a neuron, what are the three changes in permeability that occur next (in order)?

Answer 31

Sodium activation

Sodium inactivation

Potassium activation

Question 32

How can membrane depolarization be tightly controlled during an action potential?

Answer 32

Via voltage-gated channels

(ALL opened via membrane depolarization, but at different speeds –> first, Na⁺ activation, then Na⁺ inactivation, then K⁺ activation)

Question 33

Membrane polarization causes what to occur first in an action potential?

Membrane polarization causes what to occur second and third in an action potential?

Answer 33

1. Na⁺ activation (depolarization)

2. Na⁺ inactivation (repolarization)

3. K⁺ activation (repolarization)

Question 34

In an action potential, both Na⁺ and K⁺ channels will be opened.

Is there an inactivation of the Na⁺ channel?

Is there an inactivation of the K⁺​ channel?

Answer 34

Yes;

no

Question 35

In the resting state, are either of the activation or inactivation gates open on a sodium channel?

In the resting state, are either of the activation or inactivation gates open on a potassium channel?

Answer 35

Yes, the inactivation channel;

sort of - there is no inactivation gate

Question 36

Describe how a sodium channel’s activation and inactivation gates act from resting potential through an action potential and back to resting.

Answer 36

Question 37

Describe how a potassium channel’s activation and inactivation gates act from resting potential through an action potential and back to resting.

Answer 37

Question 38

If a neuron’s threshold lowers (becomes more negative), what happens to its excitability?

Answer 38

It increases

Question 39

What refractory period occurs when neuronal sodium channels first close?

What happens when they reset?

Answer 39

The absolute refractory period;

the relative refractory period

Question 40

When does the absolute refractory period end?

When does the relative refractory period end?

Answer 40

When Na⁺ channels reset;

when K⁺ channels close

Question 41

What umbrella term refers to diseases that result from defects in normal ion channel/gate function?

Answer 41

Channelopathies

Question 42

What type of Na⁺ channel inactivation occurs during an action potential?

What type of Na⁺ channel inactivation occurs between action potentials in response to new baseline resting potentials (changes in threshold / excitability)?

Answer 42

Transient inactivation;

steady-state inactivation

Question 43

Sodium channel gates open and close based off surrounding voltages.

How does steady-state inactivation of Na⁺ channels change threshold excitability?

Answer 43

Changes in baseline membrane resting potential (hyperpolarization or depolarization) can increase or decrease the number of inactivated sodium channels, thus changing a neuron’s excitability

Question 44

If you slightly depolarize a neuron (not quite to threshold) and just hold it there, what effect does this have on sodium channels in the membrane?

Answer 44

More channels are activated

(just moving up the curved line a bit in the attached graph)

Question 45

What three steps should one take in analyzing the effects of a change in ion concentration on membrane potentials?

(assuming one ion has changed)

Answer 45

1. Calculate the change in Nernst potential
2. Determine if the resting membrane potential has changed
3. Determine the effects on action potentials

Question 46

What ion’s Nernst potential is the primary factor affecting cell membrane potentials (E_m)?

Answer 46

K⁺

Question 47

What is the normal neuronal Nernst potential for Na⁺?

What will happen to this value in cases of hyponatremia?

(Use the Nernst equation)

Answer 47

+ 65 mV;

it will get closer and closer to zero

Question 48

What happens to action potentials in cases of hyponatremia?

(in terms of size and duration)

Answer 48

They have shorter peaks and longer durations

(On the attached graph, imagine an action potential taking place. The peak will be shorter and shorter as the E_{<span>Na </span>}becomes less and less)

Question 49

True/False.

All voltage-gated sodium channels are triggered at the exact same voltages.

Answer 49

False.

There is a spectrum of easy-to-stimulate and difficult-to-stimulate channels

Question 50

When is a neuron’s membrane more permeable to sodium?

When is a neuron’s membrane more permeable to potassium?

Answer 50

During depolarization in an action potential;

during repolarization and at rest

Question 51

What happens to neuron excitability in cases of hypokalemia?

Why?

(NOTE: hypokalemia refers to decreasing extracellular K⁺)

Answer 51

They become hypoexcitable (less irritable);

the cell becomes hyperpolarized –> less sodium channels are open (left graph); although, there is a greater fraction of available sodium channels for recruitment to an action potential (right graph)

Question 52

Which is more likely to affect resting membrane potential, changes in K⁺ or Na⁺?

(Assume equal changes in either)

Answer 52

K⁺

(plasma membranes are more affected by K⁺ than Na⁺)

Question 53

What effect will hypernatremia have on a cell’s resting membrane potential?

What effect will this have on action potential peaks?

Answer 53

It will become more positive;

they increase;

Question 54

Changes in ________ concentration will typically have more dramatic effects on action potential peaks.

Changes in ________ concentration will typically have more dramatic effects on resting membrane potentials.

Answer 54

Sodium;

potassium

Question 55

As extracellular potassium levels increase, the E_K moves towards or away from 0?

Answer 55

Towards

(as [K_out] / [K_in] approach 1, the equation below gets closer to the log of 1, which is 0)

Nernst equation = E_k = 60Log₁₀ ([K_out] / [K_in])

Question 56

Use the Nernst equation (see below, but try to write it yourself first) to answer the following questions:

1. What effect will hyperkalemia have on resting membrane potentials and cell excitability.

2. What effect will hypokalemia have on resting membrane potentials and cell excitability.

Nernst equation = E_k = 60Log₁₀ ([K_out] / [K_in])

Answer 56

1. Hyperkalemia = depolarization, more irritable
2. Hypokalemia = hyperpolarization, less irritable

Question 57

What is the normal neuronal Nernst potential for K⁺?

What will happen to this value in cases of hypokalemia?

(Use the Nernst equation)

Answer 57

-80 mV;

it will become more negative (hyperpolarize)

Question 58

What is the normal neuronal Nernst potential for K+?

What will happen to this value in cases of hyperkalemia?

(Use the Nernst equation)

Answer 58

-80 mV;

it will become less negative (depolarize)

Question 59

True/False.

Changing the resting membrane potential for any cell will affect the steady state Na⁺ channel curves for that cell.

(Attached below)

Answer 59

True.

Question 60

Which are more important, effects of activation or inactivation in steady-state Na⁺ channel control?

(Curves shown below)

Answer 60

Activation

Question 61

As a neuron’s threshold increases, excitability _________.

Answer 61

Decreases

Question 62

As a neuron’s threshold decreases, excitability _________.

Answer 62

Increases

Question 63

Explain why increasing amounts of extracellular K⁺ will cause increases in neuronal excitability up until a certain point where the increasing K⁺ inactivates the neurons.

(See image below)

Answer 63

First, more sodium channels are activated by the cell membrane depolarization;

at a certain point, too few channels remain available for recuitment to an action potential

Question 64

What effect does ischemia have on cell ion channels?

(Especially relevant in neurons)

What is the effect on Nernst potentials and E_m?

Answer 64

Non-specific leak of all ions;

Nernst potentials and E_m all approach 0

• (sodium channels are inactivated, depolarizing blockade)*
• (in addition, no energy is available to re-pump the ions to their correct concentrations)*

Question 65

Why does increasing extracellular potassium eventually result in smaller and smaller action potential peaks?

Answer 65

The cell’s resting membrane potential depolarizes more and more and so less and less sodium channels are available

(graph on right)

Question 66

True/False.

The amount of Ca²⁺ entering the nerve terminal is not related to the amount of neurotransmitter that is released.

Answer 66

False.

The more Ca²⁺ entering the terminal, the more product released into the synapse.

Question 67

What effect does increasing extracellular calcium have on excitable cell excitability?

Why/how?

Answer 67

It will decrease excitability;

it hinders flow through Na⁺ channels

(Note: in some cells, Ca²⁺ also opens calcium-gated K⁺ channels)

Question 68

Action potentials in the SA and AV nodes are exclusively dependent on what ion?

Answer 68

Ca²⁺

Question 69

The depolarization and plateau phases (phases 0 and 2) of ventricular action potentials are dependent on what ions?

Answer 69

Sodium and calcium

Question 70

Besides protection, what are the main functions of glial cells in terms of the extracellular neuronal environment?

Regulating:

Answer 70

[K⁺],

glutamate,

osmolytes,

etc.

Question 71

Why is it so important that glial cells tightly control extracellular K⁺ concentrations?

Why is it so important that glial cells tightly control extracellular glutamate?

Answer 71

To prevent increased cell depolarization and excitability;

same reason

Question 72

What would the value of E_m be if the permeability of the cell membrane to Na⁺ was increased, such that P_K = P_Na?

Answer 72

E_m = -15 mV

(If P_K = PNa, the new E_m lies halfway between E_K and E_Na)

Question 73

What’s the difference between an electrical synapse and a chemical synapse?

Answer 73

Electrical - gap junction flow

Chemical - neurotransmitter diffusion

Question 74

How does calcium get into nerve terminals to trigger neurotransmitter release?

How does it get back out?

Answer 74

An action potential comes down the axon and triggers voltage-gated calcium channels;

sodium-calcium exchangers, ATPase pumps

Question 75

What are some methods by which neurotransmitter is removed from the synaptic cleft?

Answer 75

Reuptake;

catabolism;

diffusion;

glial cell uptake

Question 76

What is unique about the structure of the axon in the neuromuscular junction?

What unique effect does this provide?

Answer 76

It ends in many synaptic boutons (all on one single myocyte per axon);

more neurotransmitter is released (and faster) in these synapses than any other

Question 78

Different neurotransmitters can have different effects depending on the tissue receptor on which they are acting.

For example acetylcholine is stimulatory to ___________ and inhibitory to ___________ receptors.

Answer 78

Nicotinic;

muscarinic

Question 79

What drug blocks muscarinic receptors?

What drug blocks nicotinic receptors?

Answer 79

Atropine;

curare

Question 80

One axon can synapse on how many myocytes?

Answer 80

Only one

Question 81

Why is so much neurotransmitter needed at the neuromuscular junction?

Answer 81

To go way, way above the myocyte threshold and ALWAYS produce the desired response

(you don’t want your muscles to only sometimes fire when you ask)

Question 82

In which direction do EPSPs drive the membrane potential?

Answer 82

Towards (or past) threshold

Question 83

In which direction do IPSPs drive the membrane potential?

Answer 83

Away from threshold (usually hyperpolarizing)

Question 84

An excitatory post-synaptic potential (EPSP) usually has a membrane potential of about what?

An inhibitory post-synaptic potential (IPSP) usually has a membrane potential of about what?

Answer 84

Well above threshold (typically - 5 to - 10 mV);

below threshold (often similar to E_K)

(it can even be above the resting membrane potential and depolarize the cell a bit; however, if it’s potential is below threshold, it’s inhibitory)

Question 85

Where is the highest concentration of voltage-gated sodium channels in the neuron?

Answer 85

The axon hillock

Question 86

True/False.

EPSPs and IPSPs sum in a quasi-algebraic manner.

Answer 86

True.

Question 87

The amount of neurotransmitter released from the axon terminal is directly proportional to:

Answer 87

The amount of calcium entering the axon terminal

Question 88

Do the antibodies in myasthenia gravis destroy, downregulate, or just inactivate acetylcholine-gated sodium channels?

Answer 88

Likely all three

(inactivation and destruction and downregulation)

Question 89

What is the penumbra of a stroke?

What change in membrane potential (E_m) do cells in the infarcted area undergo?

What change in membrane potential (E_m) do the penumbra cells undergo?

Answer 89

Affected tissues that are not as ischemic as the core area of the stroke;

membrane potentials dissipate (to 0 mV);

there is no large change in membrane potentials in the penumbra

Question 90

What leads to the ‘latched state’ in smooth muscle?

Answer 90

Dephosphorylation of myosin light-chain

Question 91

Via what intracellular effect does beta-adrenergic stimulation cause smooth muscle relaxation in the bronchi?

Answer 91

Increased cAMP

Question 92

Growth hormone acts especially on which layer of cartilage in endochondral ossification?

Answer 92

The reserve cartilage

Question 93

How does colchicine stabilize microtubules and inhibit synthesis?

Answer 93

By binding/sequestering tubulin dimers

Question 94

What drug inhibits interactions between leukocyte integrins and endothelial cells?

This stops T cell extravasation and may be beneficial in what disease?

Answer 94

Natalizumab;

multiple sclerosis

Question 95

Which of the following may be beneficial in treating lysosomal storage disorders:

Macromolecule dietary restrictions

Bone marrow transplant

Substrate inhibition therapy

Enzyme replacement therapy

Answer 95

Bone marrow transplant

Substrate inhibition therapy

Enzyme replacement therapy

(NOT macromolecule dietary restrictions)

Question 96

What can be given to athletes in long-term events (e.g. marathons) to slow down glycogenolysis in the liver?

Answer 96

Oral glucose

Question 97

How does repetitive nerve activity lead to short-term enhancement of neurotransmitter release?

Answer 97

Ca²⁺ accumulates in the nerve terminal