W3 - APs, nerve cells Flashcards
Which components make up the nervous system?
Give rough numbers.
- neurons that are interconnected (5k - 200k times) to form neural circuits (1011 - 1012)
- neuroglial cells (1013)
- blood bessels, connective tissue
What are the functions of the nervous system?
- gathering of information, e.g. via receptors
- transmission of information
- processing of information, e..g memory, learning, behavior
List different type of neuroglial cells + their location and briefly explain their function.
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
Explain the structure of neurons.
- 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
Which substances are transported by axonal transport?
Explain the process.
How fast is it?
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
Explain the process of axonal degeneration.
Another name.
= Wallerian degeneration
- ER distends due to protein synthesis to repair destroyed axon
- ribosomes disorganized, soma swells, nucleus eccentric position, Nissl bodies stained weakly = chromatolysis
- in CNS: myealin sheath removed by phagocytosis
in PNS: Schwann cells undergo cell division
Explain the process of axonal regeneration in the PNS.
Why does it not happen in the CNS?
- axon ending sprouts
- ending elongates into path of Schwann cells
- 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
What is the resting membrane potential?
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)
Values for ER of skeletal muscle and neurons.
- ER (sk. m.) = -90 mV
- ER (neuron) = -70 mV
What are pacemaker cells?
cells which’s EM is constantly changing, e.g. heart nodal cells
Explain the terms depolarization, repolarization, and hyperpolarization.
- depolarization: injection of positive charge, cell becomes more positive (e.g. -70 mV → -10 mV)
- repolarization: cell returns to ER
- hyperpolarization: injection of negative charge, cell becomes more negative (e.g. -70 mV → -80 mV)
What is diffusion potential?
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
What is equilibrium potential?
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
How can the equilibrium potential be calculated?
Nernst equation
describes EM when conc. on both sides of membrane are known (only 1 ion in solution)
Eion = -60/z * lg c1/c2
- z = no. of charges of ion
- c1, c2 = conc. of the 2 compartments
What are the equilibrium potentials of K+, Na+ and Cl- in skeletal muscle?
- K+: -94mV
- Na+: +65mV
- Cl-: -88mV
What are the equilibrium potentials of K+, Na+, Cl-, Ca2+ in neurons?
- K+: -90mV
- Na+: +60mV
- Cl-: -70mV
- Ca2+: +130mV
What is the membrane potential?
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 Em toward its Eq
⇒ movement of most permeable ion will have greatest effect on Em
Which formula is used to calculate the resting membrane potential?
Goldmann-Hodgkin-Katz equation
also: chord-conductance equation
- pK = permeability constant for each ion
[Cl-]ic is on the bottom because its charge is negative
Which mechanisms contribute to the resting potential of a cell?
Values.
- diffusion potential of K+: modified by other ions, can be calculated w/ GHK → 90-95% of ER
- pump potential of Na+/K+-ATPase: electrogenic transport → 3-5% of ER<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 ER
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
pK resembles opening/closure of ion channels for that particular ion
opening of K+ channels:
↑[K+]EC → entire ratio ↓ → Em becomes more positive = hyperpolarization
opening of Na+ channels:
↑pK[Na+] → pK[K+] and pK[Cl-], both negligible → Em close to ENa+ = overshooting depolarization
opening of Cl- channels:
↑pK[Cl-] → pK[K+] and pK[Na+], both negligible → Em close to ECl- = stabilization of ER (bc ER ∽ ECl-)
all assumptions refer only to the general cell behavior
Describe the structure of Na+ and K+ channels.
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)
Which substances are able to block Na+ channels?
Which substances are able to block K+ channels?
Na+ channel blockers:
- tetrodotoxin (TTX) from extracellular side (in ovaries of puffer fish)
- lidocaine (local anesthetic)
K+ channel blockers:
- tetraethylammonium (TEA+) from cytoplasmic side
Which mechanism is used by ion channels to cause non-specificity?
selectivity filter
ions can pass through pore depending on size of hydration shell surrounding the ion
e.g. only K+, no Na+
How is Ohm’s law applied to describe the electrochemical gradient?
Ohm’s law: V = R * I
⇒ Iion = gion (Em - Eion)
- V = Em - Eion
- 1/R = g = conductance, permeability
Explain the voltage clamp method.
2 microelectrodes applied into cell
- I applied, Em is set and clamped to certain value (e.g. -20 mV)
- investigated channel activated → modified Em
- compensating current applied Icomp= I that was used to modify Em
→ membrane potential can be modified independently of ionic currents ⇒
I-V relationship of ion channels can be studied
Explain the patch clamp method.
What are advantages over the voltage clamp method?
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
Explain the mechanism of an action potential w/r/t to Ohm’s law.
- localized depolarization reaches threshold potential, causes voltage dependent ion channels to open (K+ channels delayed)
- ↑ gNa+ causes positive feedback, even more Na+ channels open → depolarization
- Em approaches ENa+ → cell overshoots, doesn’t reach ENa+ bc 4)
- increasing gK+, IK+, decreasing gNa+ due to closure of inactivation gate → repolarization
- gNa+ returned to baseline levels, gK+ remains elevated → afterhyperpolarization
know the 1st 2 graphs!
Explain the gating of Na+ channels and their effect.
2 gates: activation + inactivation gate
→ 3 states: activated, inactivated, non-inactivated
- depolarization opens activation gate → activated
-
inactivation gate closes due to increased depolarization → inactivated
→ can only open after repolarization - activation gate closes
- inactivation gate opens after cell repolarized again → not-inactivated
⇒ transient increase of gNa+
What is accommodation?
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
What are the properties of action potentials?
Explain.
- 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 = ER → overshoot
What are electrotonic signals?
Explain their properties.
= 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 → Em below threshold
image shows local responses to excitatory and inhibitory pulses
Which behavior is described by the space constant?
It depends on… ?
λ = distance over which the potential change decreases to 1/e (37%)
depends on ratio of membrane resistance rm to axial resistance ra → the ↑ rm/ra, the more distant the signal transmission
⇒ ↑ in diameter of axon → ↑ rm/ra
BUT: space constant also affected by membrane capacitance (= “leakiness”, cf. myelination)
Define absolute and relative refractory period.
Why does it happen?
Consequence?
- 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
Explain the effect of myelination upon the speed of conduction.
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
What is saltatory conduction?
Explain its mechanism.
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
What is a receptor potential?
Briefly describe some ways to generate receptor potentials for different types of receptors.
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
How is the stimulus intensity coded by the AP?
↑ amplitude of receptor potentials → ↑ frequency of APs
BUT: only for suprathreshold stimuli (stimuli that exceed the threshold stimulus for an AP)
