Neurobio

Question 1

The Neuron

Answer 1

• highly specialized cell, which carries electrical information.
• understanding how a neuron works, and why it’s important to maintain electrolyte concentrations - basis of pharmacology.
• Neuron cells are post-mitotic, don’t divide
• Nervous system does have stem cells in brain to generate new neurons. But once you have a neuron, it cannot divide.

Parts of neuron:

•Cell body together with dendrites = receiving end

• Cell body is involved in integration of signals
• Pick up chemical signals (neurotransmitters), go to electrical signals (2 types), then back to chemical signal

•Axon

• Signal leaves axon hillock, and action potential travels down axon
• Sometimes the axon divides in different directions
• Myelin sheaths = Modifications on axon, affect signal

•Axon terminal leads to synapse

• Release chemical to the next neuron in chain

Question 2

Types of neurons

Answer 2

• Sensory neurons – specialized on the receiving end to receive environmental information
  
  • Ex: Cells in the retina’s rod or cone that are specialized to receive light. In the organ of cortei (sp? in ear) there are specialized hair cells that vibrate.
• Interneurons of Central Nervous System
• Efferent Neuron – typical motor neuron, innervates skeletal muscle

Question 3

Nerve vs. Neuron

Answer 3

• Neuron is single cell
• The largest neuron ever was found in a squid!
• Nerve is a cable with many neurons in it. Can see the axons of thousands of neurons. (ex: sciatic nerve)

Question 4

inputs are stimulatory or inhibatory

Answer 4

• At the receiving end, information comes in to the dendrites at the outside and directly to the cell body
• The average neuron in the CNS will receive 1000-2000 physical inputs on the receiving end
• Juggling information all the time
• some inputs are stimulatory and some are inhibatory
• some excite and lead to action potentials and others turn it off

Question 5

Glial Cells are Support Cells

Answer 5

• Ependymal cell – border areas in CNS that are next to ventricles
• Ex: there are areas in the brain where fluid moves through. Ependymal cells border ventricles of the brain.
• Oligodendrocytes – make myelin sheaths
• Myelin sheaths surround axons in the CNS. By doing that, they change the electrical properties.
• Microglia – cells from immune system that help to clear up dead material. “Police” areas.
• Astrocytes – usually found around synapses. Have various roles, including regulation of potassium ion channels
• Whereas neuron cells are post-mitotic, glial cells are not and can divide
• Brain cancers arise from things that go round in glial cell division

Question 6

When myelin sheaths not working

Answer 6

• Ex: multiple sclerosis when myelin sheaths in brain deteriorate. Or diabetic patients may lose sensation in feet because myelin is not properly laid down.
• Changes the capacitance and resistance in the axon

Question 7

Peripheral NS

Answer 7

•Schwann cells – wrap around axons in the PNS

• Form the myelin sheath in the periphery. (Counterpart to oligodendrocytes)

•Nodes of Ranvier – spaces between myelin sheath

• Spaced evenly along the axon, where you have unmyelinated axon

•Satellite cells – support cell bodies. We’re not quite sure what they do.

Question 8

Glial Cells in PNS and CNS

Answer 8

wont be tested but know

Question 9

Action Potential

Answer 9

• all or nothing
• charged atoms are responsible for electrical phenomenon
• selectively permeable membrane, ions can only move through channels
  
  • K+ concentration is kept high inside cell
  • Na+ and Cl- kept high outside cell
  • ion channels responsive to potential difference aka voltage across membrane
    
    • voltage gated ion channels - there’s a threshold Energy_threshold on graph

Question 10

Neuron at rest vs. AP

Answer 10

• at rest: permeability for K+ is greater than permeability for Na+ at rest
  
  • K+ diffuses outside cell taking + charge w/it leaving neg charge inside cell
• during action potential: ion channels for Na+ open, higher permeability than K+
  
  • Na+ diffuses into cell, takes + charges with it briging cell up to +35 mV
  • depolarization is due to > in conductance (g) to Na+
  • repolarization is due to > in conductance (g) to K+

Question 11

At peak of graph, 2 things occur

Answer 11

• K+ channels open (increased conducance of K+ which means repolarization)
• and Na+ channels are inactivated
• Na+ actively inactivates, and K+ channels don’t

Question 12

3 values to memorize

Answer 12

• K+: 120 mM on inside, 4 mM on outside
• Na+: 14 mM on inside, 140 mM on outside
• Cl-: 4 mM on inside, 105 mM on outside

ion distribution is basis for electrical activity

Question 13

Ion Distribution is Key - what is responsible for that?

Answer 13

Requires energy. 3 experiments helped to show that this is not passive:

1. Axon at 4 degrees Celsius, when there is virtually no metabolism. The Resting Membrane Potential (RMP) was 0 mV. This suggested that a metabolic event was required.
2. Na+22. Put radioactive sodium on the outside of an axon at rest. It slowly showed up on the inside of the cell – “the sodium leak”. (Sodium isn’t perfectly impermeable at rest, there’s a little leak. If sodium kept leaking in over time, resting membrane potential would go to 0.)
3. Oubain. It poisons the Na+/K+ pump, lose ion distribution, lose excitable cells. So if we use oubain, the RMP goes to 0 mM.

Question 14

Electrical and Chemical Gradient

Answer 14

• use Na+/K+ exchange pump to set up this electrochemical gradient; uses ATP to pump against gradient
  
  • 3 Na+ outside the cell for every 2 K+ it moves inside the cell; So it moves 3 charges outside, 2 inside.
• contributes to the electrical charge gradient, so that inside overall is negative compared to outside, making the pump “electrogenic”
  *

Question 15

Why is RMP at -70?

Answer 15

• b/c of electrical/chemical equilibrium across the cell
• There is a chemical diffusion force on the ions. The ions also have an electrical force, since it has a charge
• b/c K+ channels are open: K+ diffuses out, taking positive charges with it, leaving inside electronegative enough so:
  • inside neg enough that + charges held from leaving so no net diffusion b/c chemical forces on ion = electrical forces on ion
  • Nerst helps find this equilibrium pt
    
    • This is why Resting Membrane Potential = -70 mV

Question 16

Nernst Equation - helps find equilibrium

Answer 16

• pt where chemical diffusion forces on ion = electrical forces on ion
• at rest K+ is most permeable ion so membrane potential follows most permeable ion
• RMP is -70 not -85 b/c other ions are involved but K+ biggest role
• If you start changing the concentration of potassium, you change its equilibrium potential, which changes the resting membrane potential, which wreaks havoc on electrical system
• At -85 mV, the electrical potential and chemical diffusion forces are equal and opposite, and there’s no net diffusion
• However, at rest, the reason the membrane potential is about -70 is because potassium is the most permeable ion across the membrane at rest, and potassium will be the most likely ion to reach its equilibrium potential. Therefore, the Resting Membrane Potential follows the potassium equilibrium potential.

Question 17

Change K+ in/out of cell:

higher K+ out of cell

Answer 17

• higher K+ out of cell, RMP becomes closer to zero so less gradient so RMP moves closer to zero since K+ sets RMP
• if it resets too high - not enough gradient, then cell can’t fire b/c channels are voltage gated; so Na+ voltage gated channels won’t work
• bollast of K+ kills nerves because K+ elevated outside of cells prevents firing since change in RMP
• if K+ out is low, harder to bring cell to AP b/c RMP is even more neg

Question 18

Why does the AP go to +40?

And where does conductance shut off?

Answer 18

• during AP, Na+ is MOST PERMEABLE ion
• Na+: E_Na+ = +65 in our system
• membrane potential moves toward Na+ potential and Na+ gates inactivate at +35, so cut short and gates begin to close
• conductance shuts off at peak of graph which is called inactivation
  
  • increase in K+ to bring RMP back down
  • K+ respons for RMP which is why its -70: electrochemical gradient and K+ high on inside and diffuses across gradient, sets up electrical gradient that is equal and opposite neg force

Question 19

Sodium Leak

Answer 19

• at rest, there’s a bit of Na+ leak which affect RMP which is part of why RMP not quite at -85

Question 20

Goldman Equation

Answer 20

• describes the MP
• in over out for Na and K
  
  • reversed for CL since neg ion; out over in for Cl
• if there’s little Na+ leak then + charges are going to accumulate inside cell which changes RMP a bit so important we pump out w/ATP pump

Question 21

Manipulate Na+ in and out of cell

Answer 21

• lower Na+ concentration outside cell
  
  • weaker diffusion gradient since less electrical force to hold Na+, so electrical Na+ equals about 20, so less high
• heart stops and cardiac cells lyse and untraceable since cant’ tell K+ inside or outside cell

Question 22

AP looked at Electrically via Ohm’s Law

Answer 22

• V= IR where R = resistance or 1/g where g = conductance/permeability
  
  • I = EMF x g where EMF is force on ion
  • V = EMF = membrane potential - ion potential
• voltage gated ion channels respond to change in voltage in membrane
• current flow for K+:
  
  • high current flow for K+ on other side of AP and overshoot RMP and shoot for K+ equilibrium
• experiment - axon put electrode on it and suck up Na+ ion channel and see electrophysiology little diff for each one
• conductivity of K+ channels go down when L side of graph and then some are very sensitive to AP and open up
  
  • shape of AP determined by timing of opening and closing channels and how conductance changes
• inactivation pt is peak of Na+
  
  • k+ peaks following Na+ explosion

Question 23

Current K+ at AP peak vs. Na+ current at AP peak

Answer 23

• high current flow for K+ on other side of AP and overshoot RMP and shoot for K+ equilibrium
  
  • since EMF membrane at AP is 35 and Ek+ = -85 and conductance is high at AP since K+ channels open at AP so high g meaning :
  • current for K+ at AP peak is high!
• at rest:
  
  • K+ is most permeable ion so g not low but low EMF so some flow of K+
• at threshold:
  
  • low flow since emf not high and g is overcome by Na+ flow
• at overshoot:
  
  • no net flow since emf = zero since going to -85 for a sec and therefore no net K+ current
• very low current flow at AP peak for Na+
  
  • since EMF = +35 -+65 x g (very low - since Na+ are closing completely)
  • so current = low since I = EMF x g

Question 24

Current of Na+ at rest and then at threshold peak

Answer 24

at rest:

• EMF x g = I where EMF = Emembrane - Ena+
• -70 - +65 x g (conductance is very low since not opening Na+ voltage gated channels yet and at RMP)
• so low current of Na+ at rest; only leakage

at threshold potential:

• current na+ = -60 - +65 x g (high conductance at threshold when open Na+ gates)
• so very high current of Na+ since when starting AP is at threshold potential

at AP:

very low flow of Na+ since low EMF and Na+ channels are closing so low conductance

Question 25

Propagation - AP starts in axon and gets propagated down axon - How?

Answer 25

• stimulus changes charge at small area of membrane
• positive K+ moves to negative area right next to where original change occurred to generate local current flow
  
  • if enough of this occurs then voltage gated-ion channels for Na+ open
  • positive Na+ flows in and moves to negative charge inside cell displacing positive charge outside and so on
• AP sets up current flow; local current flow sets up next AP, which sets up local current flow –> propagation
• in body, local current flow just one direction since at axon hillicle since voltage gated Na+ channels to R but not L (no AP to conduct)
  
  • additional stimulus wont’ give you an AP, so AP only goes in one direction
    
    • wont get another AP - absolute refractory period
    • if you give it more than normal you can probably get it to fire - relative refractory period

Question 26

Refractory Period

Answer 26

• necessary to repolarize (re-establish +/-) across the membrane so can’t fire AP again yet
• additional stimulous won’t give you an AP so only in 1 directino
• relative refractory period is if you give it more than normal you can get it to fire

Question 27

Glial Cells

Answer 27

• have myelin sheath and node of Raniar
• myelination > velocity of conduction and best way to > velocity
  
  • changes in electrical properties around neuron by > resistance and < capacitance
    
    • K+ moves to area w/more concentration of - charge away from myelin
      
      • local current flow moves quickly to node where greater - charge
    • therefore AP jumps saltatery conduction
  • increase diameter can also > velocity but not as much as myelination
• motor neurons and CNS myelinated but pain unmyelinated

Question 28

Myelinated to unmyelinated

Answer 28

• more current flow in same distance for myelinated
• length constant - where you lose 2/3 of current flow