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)