Lec 3 & 4 - Ion Channels and Membrane Potential

Question 1

During action potential, the direction of net flux of potassium ions during repolarization and of sodium ions during depolarization are respectively,

a) outward, outward
b) inward, inward
c) inward, outward
d) outward, inward
e) no net flux, outward

Answer 1

c) inward, outward

Question 2

A 53 year-old HIV positive African American male experiences severe generalized muscle weakness, tiredness, and difficulty in mastication for two days following his air conditioning breakdown that occurred 5 days ago. During the last week, he consumed a lot of orange juice to quench his thirst. His friend drives him to a hospital where he is diagnosed with acute renal failure. His lab shows hyperkalemia. His symptoms disappear when his blood potassium was normalized. An increase in which of the following is most likely associated with his muscle weakness?

a) conductance of fast sodium channels
b) conductance of neuromuscular axons
c) refractory period for action potential generation
d) absolute value of equilibrium potential for potassium
e) magnitude of the neuronal membrane potential

Answer 2

c) refractory period for action potential generation

Muscle weakness indicates that the refraction periods that precede action potential generation became longer in the patient. This occurs bc sodium channels are prone to inactivation in sustained hyperkalemia, decreasing probability of axonal impulse discharge. A stronger stimulus will be necessary to induce an action potential and periods of neuronal silence will increase. Conductance of fast sodium channels is reduced during hyperkalemia due to their accommodation (inactivation). Axonal conductance of action potentials can be only slower. In accordance with the Nernst equation and due to a shift of the neuronal membrane potential towards 0 (depolarization), hyperkalemia will result in a decreased absolute value of equilibrium potential for potassium and magnitude of the neuronal membrane potential.

Question 3

Digoxin, a cardiac glycoside, is used to treat heart failure. ITs action is based on inhibition of sodium/potassium ATPase. Which of the following is most likely followed digoxin treatment?

a) depolarization of the excitable cells
b) increased antidromic saltatory conduction
c) decreased risk of corneal edema
d) gain in electrochemical potential that drives Na+ into cells
e) cell membrane potential shift towards equilibrium potential for K+

Answer 3

a) depolarization of the excitable cells

Activity of the sodium potassium pump tend to hyperpolarize cells (3 Na+ ions out and 2 K+ ions in). Its inhibition has an opposite effect and does not shift cell membrane potential towards equilibrium potential for K+ which is approximately - 90 mV. Antidromic saltatory conduction may occur in partially demyelinated fibers, but can not be caused by digoxin. The drug promotes corneal edema by inhibiting endothelial water removal from the stoma. The electrochemical potential (or gradient, a sum of concentration and electrical forces) that acts upon Na_ ions and determines their ability to move into cells will be reduced because of the gain of positive charge inside neurons after sodium potassium ATPase inhibition.

Question 4

T/F - The flux of molecules transported across the cell membrane by simple diffusion increases proportionally with a substrate concentration, whereas a carrier mediated transport reaches its maximum (Tmax).

Answer 4

True

Question 5

What technique allows monitoring of the activity of a single ionic channel?

Answer 5

Patch clamp technique

Question 6

What is Ohm’s law?

Answer 6

V (voltage) = I x R

I = current
R = resistance - pore restriction on ion movement, difficulty that an ion has moving through a pore

R= 1/g 
g = conductance - ease at which the ion moves through a pore

Question 7

How can resistance be increased?

Answer 7

Application of ion channel blockers like local anesthetics

Question 8

What must be achieved in order to have an equilibrium state?

Answer 8

Chemical potential (force due to concentration gradient of permeable ion) = - Electrical Potential (force due to charge separation across membrane)

This means there is no net flux of ions.

Question 9

What are the forces acting on ions?

Answer 9

1. Chemical gradient
2. Electrical gradient
3. Electrochemical potential (effect of both forces on an ion)

Dependent on both concentration and voltage

Question 10

What ions are of higher concentration inside the cell? outside?

Answer 10

Inside = K+
Outside = Na+, Ca2+, Cl-

Question 11

T/F - All body cells have a resting membrane potential.

Answer 11

True - All have negative charge on the intrinsic surface of the cell membrane.

Question 12

Is the resting membrane potential of excitable cells (neurons and muscle cells) higher or lower than other cells?

Answer 12

Higher (more negative Vm)

Ex: non-excitable cells like parotid gland Vm = -30
Ex: excitable cells like neurons Vm = -90

Question 13

Cell membrane potential shifts towards Vk (equilibrium potential for potassium ion) during ____________________.

Answer 13

Hyperpolarization

Question 14

Cell membrane potential approaches VNa (equilibrium potential for sodium ion) at the peak of __________________.

Answer 14

Depolarization (upstroke)

Question 15

At rest, the cell membrane potential is primarily determined by what ions?

Answer 15

K+ (potassium)

Question 16

What causes Vm to be slightly less negative than Vk?

Answer 16

Small Na+ “leaks”

Question 17

What are the two factors that maintain resting membrane potential?

Answer 17

1. Unequal distribution of ions across the cell membrane due to relative impermeability of the membrane for Na and K ions
2. Activity of Na-K ATPase (20%)

Question 18

Oxygen deprivation of the cornea inhibits Na/K pump and results in stromal ________.

Answer 18

Edema (swelling)

Question 19

How does changes in potassium concentration affect the neuronal membrane potential?

Answer 19

It can cause hyperpolarization or depolarization due to K+ movement into or out of cell.

Question 20

Upon rising of extracellular concentration of K+ from 4 mM to 12 mM the membrane potential of sensory neurons that project to the teeth will become:

a) less negative (depolarize)
b) More negative (hyperpolarization)
c) unchanged
d) nobody knows but Nernst

Answer 20

a) less negative (depolarization)

Question 21

How does high extracellular potassium affect the chemical gradient?

Answer 21

It promotes conservation of positive charges inside the cells decreasing efflux of potassium through the “leaking” channels. For example, hyperkalemia causes depolarization of excitable cells.

Question 22

T/F - Action potentials can be generated in all cells.

Answer 22

False - only excitable cells - neurons, skeletal and smooth muscle

Question 23

What is the difference between graded potentials and action potentials?

Answer 23

Graded potentials are local signals within cells whereas, action potentials serve as distant signals for communication between cells.

Question 24

T/F - Hyperpolarization and sustained profound depolarization decreases excitability of neurons.

Answer 24

True

Question 25

What occurs during the rising phase of an action potential?

Answer 25

Upstroke / Depolarization

A stimulus causes Na+ channels to open. Threshold is reached and Na+ influx due to high conductance drives depolarization as the membrane potential reaches its peak positive value

Question 26

What occurs during the falling phase of an action potential?

Answer 26

Repolarization

Na+ channels undergo inactivation and Na+ influx stops. K+ channels open slowly and K+ flows out of the cell driving membrane potential back to negative value.

Question 27

What occurs during the undershoot phase of an action potential?

Answer 27

Hyperpolarization

K+ channels are closing and K+ outflux, which drives hyperpolarization as the cell membrane approaches its equilibrium potential for K+ decreases.

Question 28

Does firing of an action potential require a huge passage of ions across the cell membrane?

Answer 28

No. A very small net charge (10^-16 moles) must be moved across the cell membrane to create a voltage change of about 100 mV (action potential). It means that neurons can fire action potentials for hours without disturbing its electrolyte balance.

Question 29

Compared to the resting condition the undershoot is characterized by a significantly increased:

a) membrane conductance to sodium
b) cell osmolarity
c) cell excitability
d) membrane resistance to potassium
e) magnitude of the membrane potential

Answer 29

e) magnitude of the membrane potential

Question 30

Na+ channels have two gates. What are they called?

Answer 30

Activation gate and inactivation gate

Question 31

What are the 3 states the Na+ channel gates can exist in?

Answer 31

Resting (activation gate closed), conducting (both gates open), and inactivated (inactivation gate closed).

Question 32

T/F Normal moderate and short lasting depolarization typically increases cellular excitability and facilitates firing of action potentials.

Answer 32

True

Question 33

What is responsible for analgesic effect of K+ rich Sensodyne tooth paste?

Answer 33

Na+ accomodation - It is thought that K+ ions depolarize the sensory nerves, thus, inactivating Na+ channels and blocking pain transmission.

Question 34

What are the affects of hypercalcemia on action potential thresholds?

Answer 34

High levels of Ca2+ elevates the thrshold of peripheral axons and makes them less excitable. In contrast though, excitability and contractility of cardiac cells is increased by hypercalcemia.

Question 35

What is the pathway in which local anesthetics work?

Answer 35

Local anesthetics like novocaine or cocaine bind to Na+ channels and inhibiting opening of the channel. This leads to reduced numbers of action potentials and a lack of pain perception. This also occurs with the chemical tetrodotoxin from a puffer fish.

Question 36

Can a second action potential occur during the rising phase of an action potential?

Answer 36

No

Question 37

During a relative refractory period have inactivation of Na+ channels occurred?

Answer 37

Yes

Question 38

How long is the absolute refractory period (depolarization peak)? relative refractory peak (hyperpolarization)?

Answer 38

absolute refractory period = 0.5 ms

relative refractory period = 3 ms

Question 39

What period sets the maximum rate at which the cell can fire action potentials?

Answer 39

Refractory

Question 40

Long/Short refractory periods of cardiomyocytes are important for proper heart contraction and prevention of ventricular fibrillation.

Answer 40

Long

Question 41

What two factors influence the speed of AP propagation?

Answer 41

Axon size - larger axon conduct current faster

Myelination - dramatically increases conduction velocity

Question 42

What are the cells of myelination in CNS and PNS?

Answer 42

CNS - oligodendrocytes

PNS - schwann cells

Question 43

What are the Nodes of Ranvier and what is concentrated here?

Answer 43

They are the gaps between the myelin coverings and there are Na+ channels concentrated here. This arrangement results in saltatory conduction (AP leaps from node to node).

Question 44

What is an example of a disease in which there is severe demyelination of axons?

Answer 44

Multiple sclerosis - this leads to blockage of action potential conduction. Multiple sclerosis can affect optic nerve causing deterioration of vision and can cause orbital pain. The symptoms usually worsen during exercise and exposure to hot temperature (Uhthoff Sign).

Question 45

Is the retinal portion of an axon usually myelinated or unmyelinated?

Answer 45

Unmyelinated - if it is myelinated, it is usually asymptomatic although sometimes is associated with decreased vision, myopia, amblyopia, especially with very large areas and densities of myelination.