W3 - APs, nerve cells

Question 1

Which components make up the nervous system?

Give rough numbers.

Answer 1

• neurons that are interconnected (5k - 200k times) to form neural circuits (10¹¹ - 10¹²)
• neuroglial cells (10¹³)
• blood bessels, connective tissue

Question 2

What are the functions of the nervous system?

Answer 2

• gathering of information, e.g. via receptors
• transmission of information
• processing of information, e..g memory, learning, behavior

Question 3

List different type of neuroglial cells + their location and briefly explain their function.

Answer 3

in the CNS:

• astrocytes: regulate microenvironment, mediate entry of substances into CNS (K⁺, neurotransmitters), form glial scar after injury
• oligodendrocytes: one cell forms myelin sheath for many axons of diff. neurons
• microglia: latent phagocytes
• ependymal cells: specialized ependymal cells in choroid plexus secrete CSF, epithelial layer

​in the PNS:

• Schwann cells: each cell forms myelin sheath for one section of the axon
• satellite cells: encapsulate dorsal root + cranial n. ganglion cells, regulate microenvironment

Question 4

Explain the structure of neurons.

Answer 4

• dendrites: convey information to cell body, account for 90% of surface area, amount + shape dependent on type of neuron, well developed cytoskeleton
• cell body (perikaryon, soma): contains Nissl bodies (rER), prominent golgi, nucleus/nucleolus for protein synthesis
• axon: output of neuron, may have arborization (branches), arises in axon hillock (↑ Na⁺ channels, lacking organelels)
• axon terminal: forms presynaptic terminal

Question 5

Which substances are transported by axonal transport?

Explain the process.

How fast is it?

Answer 5

motor proteins moving along the microtubule

• fast axonal transport for membrane bound organelles = 50-400 mm/d
• slow axonal transport for proteins = 1-10mm/d

either:

• anterograde w/ aid of kinesins: e.g. synaptic vesicles + enzymes resp. for synthesis of neurotransmitters
• retrograde w/ aid of dyneins: e.g. recycled synaptic vesicle membrane for lysosomal digestion

Question 6

Explain the process of axonal degeneration.

Another name.

Answer 6

= Wallerian degeneration

1. ​ER distends due to protein synthesis to repair destroyed axon
2. ribosomes disorganized, soma swells, nucleus eccentric position, Nissl bodies stained weakly = chromatolysis
3. in CNS: myealin sheath removed by phagocytosis
   in PNS: Schwann cells undergo cell division

Question 7

Explain the process of axonal regeneration in the PNS.

Why does it not happen in the CNS?

Answer 7

1. axon ending sprouts
2. ending elongates into path of Schwann cells
3. reinnervate original peripheral target structure

happens at speed of ∽ 1 mm/d

in CNS axons also sprout, but oligodendrocytes do not form path, also formation of glial scar by astrocytes

Question 8

What is the resting membrane potential?

Answer 8

potential difference between the intra­ and extracellular space when a cell is at rest (i.e., it is between action potentials, not performing any special function)

Question 9

Values for E_R of skeletal muscle and neurons.

Answer 9

• E_R (sk. m.) = -90 mV
• E_R (neuron) = -70 mV

Question 10

What are pacemaker cells?

Answer 10

cells which’s E_M is constantly changing, e.g. heart nodal cells

Question 11

Explain the terms depolarization, repolarization, and hyperpolarization.

Answer 11

• depolarization: injection of positive charge, cell becomes more positive (e.g. -70 mV → -10 mV)
• repolarization: cell returns to E_R
• hyperpolarization: injection of negative charge, cell becomes more negative (e.g. -70 mV → -80 mV)

Question 12

What is diffusion potential?

Answer 12

potential difference generated across a membrane when an ion diffuses down its concentration gradient

BUT: equilibration → only transient

• magnitude depends on concentration gradient
• sign depends on charge of diffusing ion

Question 13

What is equilibrium potential?

Answer 13

transmembrane voltage of a particular ion at which the influences of concentration gradient and electrical gradient on the ion’s movement exactly balance each other out

⇒ no net movement of the ion across the membrane

Question 14

How can the equilibrium potential be calculated?

Answer 14

Nernst equation
describes E_M when conc. on both sides of membrane are known (only 1 ion in solution)

E_ion = -60/z * lg c₁/c₂

• z = no. of charges of ion
• c₁, c₂ = conc. of the 2 compartments

Question 15

What are the equilibrium potentials of K⁺, Na⁺ and Cl^- in skeletal muscle?

Answer 15

• K⁺:­ -94mV
• Na⁺: +65mV
• ­Cl^-:­ -88mV

Question 16

What are the equilibrium potentials of K⁺, Na⁺, Cl^-, Ca²⁺ in neurons?

Answer 16

• K⁺:­ -90mV
• Na⁺: +60mV
• ­Cl^-:­ -70mV
• Ca²⁺: +130mV

Question 17

What is the membrane potential?

Answer 17

in a complex system w/ mulitple ions

permeant ions diffuse across the membrane down their concentration gradients (established by prim./sec. active transport mech.)

→ each ion “wants” to drive the E_m toward its E_q
⇒ movement of most permeable ion will have greatest effect on E_m

Question 18

Which formula is used to calculate the resting membrane potential?

Answer 18

Goldmann-Hodgkin-Katz equation
also: chord-conductance equation

• p_K = permeability constant for each ion

_{[Cl-]ic is on the bottom because its charge is negative}

Question 19

Which mechanisms contribute to the resting potential of a cell?

Values.

Answer 19

• diffusion potential of K⁺: modified by other ions, can be calculated w/ GHK → 90-95% of E_R
• pump potential of Na⁺/K⁺-ATPase: electrogenic transport → 3-5% of E_{R<br></br> bc electrogenic (3Na+ out, 2K+ in, also: est. conc. gradient of K+)}
• Donnan potential: bc of neg. charged proteins that remain in IC space → 2% of E_R

Question 20

Describe the effects of these events w/r/t the GHK (Goldmann-Hodgkin-Katz equation):

• the opening of K⁺ channels
• the opening of Na⁺ channels
• the opening of Cl^- channels

Answer 20

p_K resembles opening/closure of ion channels for that particular ion

opening of K⁺ channels:

↑[K⁺]_EC → entire ratio ↓ → E_m becomes more positive = hyperpolarization

opening of Na⁺ channels:

↑p_K[Na⁺] → p_K[K⁺] and p_K[Cl^-], both negligible → E_m close to E_Na⁺ = overshooting depolarization

opening of Cl- channels:

↑p_K[Cl^-] → p_K[K⁺] and p_K[Na⁺], both negligible → Em close to E_Cl^- = stabilization of E_R (bc E_R ∽ E_Cl^-)

_{all assumptions refer only to the general cell behavior}

Question 21

Describe the structure of Na⁺ and K⁺ channels.

Answer 21

Na⁺ channels:

• β₁, β₂ subunit
• α subunit: 4 six transmembrane helices that form the wall of the pore
• voltage-gated (activation gate + inactivation gate)

K⁺ channels:

• 4 six-transmembrane helices
• voltage-gated (1 gate)

Question 22

Which substances are able to block Na⁺ channels?

Which substances are able to block K⁺ channels?

Answer 22

Na⁺ channel blockers:

• tetrodotoxin (TTX) from extracellular side (in ovaries of puffer fish)
• lidocaine (local anesthetic)

K⁺ channel blockers:

• tetraethylammonium (TEA⁺) from cytoplasmic side

Question 23

Which mechanism is used by ion channels to cause non-specificity?

Answer 23

selectivity filter

ions can pass through pore depending on size of hydration shell surrounding the ion

e.g. only K⁺, no Na⁺

Question 24

How is Ohm’s law applied to describe the electrochemical gradient?

Answer 24

Ohm’s law: V = R * I

⇒ I_ion = g_ion (E_m - E_ion)

• V = E_m - E_ion
• 1/R = g = conductance, permeability

Question 25

Explain the voltage clamp method.

Answer 25

2 microelectrodes applied into cell

1. I applied, E_m is set and clamped to certain value (e.g. -20 mV)
2. investigated channel activated → modified E_m
3. compensating current applied I_comp= I that was used to modify E_m

→ membrane potential can be modified independently of ionic currents _​⇒
I-V relationship of ion channels can be studied

Question 26

Explain the patch clamp method.

What are advantages over the voltage clamp method?

Answer 26

1 microelectrode applied on cell membrane close to ion channel

⇒ localized voltages that are necessary to open the ion channel can be measured

advantages:

• non-invasive
• close spatial relation avoid measurement of leak channels

Question 27

Explain the mechanism of an action potential w/r/t to Ohm’s law.

Answer 27

1. localized depolarization reaches threshold potential, causes voltage dependent ion channels to open (K⁺ channels delayed)
2. ↑ g_Na⁺ causes positive feedback, even more Na⁺ channels open → depolarization
3. Em approaches E_Na⁺ → cell overshoots, doesn’t reach E_Na⁺ bc 4)
4. increasing g_K⁺, I_K⁺, decreasing g_Na⁺ due to closure of inactivation gate → repolarization
5. g_Na⁺ returned to baseline levels, g_K⁺ remains elevated → afterhyperpolarization

_{know the 1st 2 graphs!}

Question 28

Explain the gating of Na⁺ channels and their effect.

Answer 28

2 gates: activation + inactivation gate
→ 3 states: activated, inactivated, non-inactivated

1. depolarization opens activation gate → activated
2. inactivation gate closes due to increased depolarization → inactivated
   → can only open after repolarization
3. activation gate closes
4. inactivation gate opens after cell repolarized again → not-inactivated

⇒ transient increase of g_Na⁺

Question 29

What is accommodation?

Answer 29

too slow depolarization → threshold potential passed w/o AP being fired

bc: critical no. of Na⁺ channels required to trigger an AP cannot be reached due to inactivation

Question 30

What are the properties of action potentials?

Explain.

Answer 30

• all-or-none: does not occur if depolarization passes threshold pot. too slowly
• regenerating: localization induces new action potential
• spreads w/o decrement: mechanism of AP does not change during propagation
• unidirectional
• high amplitude = E_R → overshoot

Question 31

What are electrotonic signals?

Explain their properties.

Answer 31

= local subthreshold respones

• graded: either excitatory, (cf. EPSP) or inhibitory (cf. IPSP)
• localized + spreads w/ decrement: potential change depends on proximity to site of passage of current, indicated by space constant λ
• low amplitude = E → E_m below threshold

_{​image shows local responses to excitatory and inhibitory pulses}

Question 32

Which behavior is described by the space constant?

It depends on… ?

Answer 32

λ = distance over which the potential change decreases to 1/e (37%)

depends on ratio of membrane resistance r_m to axial resistance r_a → the ↑ r_m/r_a, the more distant the signal transmission

⇒ ↑ in diameter of axon → ↑ r_m/r_a

BUT: space constant also affected by membrane capacitance (= “leakiness”, cf. myelination)

Question 33

Define absolute and relative refractory period.

Why does it happen?

Consequence?

Answer 33

• absolute: cell is unable to fire a second AP due to inactivation of Na⁺ channels, independent of strength of stimulus
• relative: cell able to fire a second AP, but stronger stimulus than original one required bc some Na⁺ channels still inactivated

⇒ limit maximal frequency of conducting APs to 500-1000 Hz

Question 34

Explain the effect of myelination upon the speed of conduction.

Answer 34

oligodrendrocytes (CNS), Schwann cells (PNS) form myelin layers around axons w/ nodes of Ranvier (∽ 1μm) in between

⇒ decrease capacitance of axon membrane (“less leaky”) → increased space constant + speed of conduction

for physiological explanation cf. saltatory conduction

Question 35

What is saltatory conduction?

Explain its mechanism.

Answer 35

APs jump from each node of Ranvier to the next

mechanism:

• myelination causes charge seperation of ions → electrotonic conduction btw nodes of Ranvier
• nodes of ranvier lack K⁺ channels, but show large amount of Na⁺ channels → no afterhypolarization
• BUT: Na⁺/K⁺-ATPase needed to extrude Na⁺ that enters, reaccumulates K⁺ inside

Question 36

What is a receptor potential?

Briefly describe some ways to generate receptor potentials for different types of receptors.

Answer 36

stimulus of a sensory receptor as a response to an external or internal event

• chemoreceptor: chemical stimulant binds to receptor molecule → opening of ion channel + ionic current influx
• mechanoreceptor: mechanical force distorting the membrane of the receptor → opening of ion channel + ionic current influx
• photoreceptor: ion channel open in the dark, closed when photon absorbed → influx of current stops + hyperpolarization

_{REMEMBER: sensory neurons are pseudounipolar, hence produced receptor potential transduced to axon}

Question 37

How is the stimulus intensity coded by the AP?

Answer 37

↑ amplitude of receptor potentials → ↑ frequency of APs

BUT: only for suprathreshold stimuli (stimuli that exceed the threshold stimulus for an AP)