ET: Neurons

Question 1

Structure of a Neuron

Answer 1

• Soma (cell body)
• Dendrites
• Usually a single axon

Question 2

Electrical Signals

Answer 2

• Input

- Dendrites, cell body, axon

Question 3

Chemical Signals

Answer 3

• Output

- Synapses

Question 4

Resting Membrane Potential (RMP)

Answer 4

• Voltage measured across a cell membrane
• Typically -65mV
• Potential out of the cell is defined as 0
• Can be measured with intracellular micro electrodes or patch-clamp pipettes
• Based on differences in concentration of Na+ and K+ inside and outside of the cell
• The differences in permeability of cell membrane to these ions
• Electrogenic action of Na/K Pump (small)

Question 5

Channels affecting permeability

Answer 5

1. Non-gated channels (leak) that are open at rest
   - In Glia cells the RMP almost entirely depends on leak K+ channels
2. Gated-channels (voltage or ligand) which are closed at rest

Question 6

Rest Permeability of K:Na

Answer 6

P(K):P(Na) = 40:1

- Steady diffusion of K+ into the cell and Na+ out of the cell

Question 7

Glass Micro electrode technique

Answer 7

Glass electrodes with a very fine tip filled with a concentrated salt solution can be inserted into a neuron membrane to read the voltage changes

Question 8

Patch-Clamp technique

Answer 8

Patch pipette is larger and only can touch the outside of the neuron membrane
- Uses negative pressure pulse to break and then reseal the membrane to measure current and voltage

Question 9

Concentration of Na+ and K+ outside the cell

Answer 9

Na+ outside = 150mM

K+ outside = 5mM

Question 10

Concentration of Na+ and K+ inside the cell

Answer 10

Na+ inside = 15mM

K+ inside = 100mM

Question 11

Equilibrium Potential

Answer 11

When net flow of ions is 0 in spite of concentration gradient and permeability
- Nernst Equation is used to calculate equilibrium potential for each individual ion that contributes to RMP

Question 12

Nernst Equation

Answer 12

Nernst Equation is used to calculate equilibrium potential for each individual ion that contributes to RMP

• Only applicable wen the cell membrane is permeable to only one ion (e.g. glia cells only have for K+)
• No permeability included

E(ion) = 2.3 x (RT/zF) x log ([ion]o/[ion]i)

Question 13

Nernst Equation for K

Answer 13

E(K) = 61.5mV x log ([K+]o/[K+]i)

Ek = -80mV

Question 14

Nernst Equation for Na

Answer 14

E(Na) = 61.5mV x log ([Na+]o/[Na+]i)

Ek = +60mV

Question 15

RULE 1

Answer 15

The higher the permeability of the cell membrane to a particular ion, the greater the ability of this ion to shift the RMP towards its equilibrium potential

Question 16

Goldman Equation

Answer 16

Method for calculating the value of RMP taking into account both the concentration gradient and relative permeability of the resting cell membrane to K+ and Na+

Vm = 61.5mV x log{ (Pk[K+]o + Pna[Na+]o) / (Pk[K+]i + Pna[Na+]i) }

Question 17

Action Potential (AP)

Answer 17

• Brief fluctuation in membrane potential

- Information is coded in the frequency of AP

Question 18

4 Stages of an AP

Answer 18

1. Depolarisation to threshold
   - Cell membrane is depolarised from around -65mV to -55mV by a physical (electric current, light, stretch) or chemical (drug or synaptic excitation) stimulus
   - Depolarisation to threshold is evoked by Excitatory Post Synaptic Potentials (EPSP’s) which spread passively from dendrites
   - Voltage gated Na+ channels begin to open
2. Fast depolarisation (toward ENa+)
   - MP moves from around -55mV to around +30mV
   - Voltage gated Na+ channels open allowing fast influx of Na+ into the cell
3. Repolarisation (toward EK+)
   - Inactivation of Na+ channels and activation of voltage-gated K+ channels
   - Bringing MP down below starting (below -65mV)
4. After hyper polarisation (AHP)
   - Returns to RMP

Question 19

Absolute Refractory Period

Answer 19

• Stages 2 and 3 of an AP
• Has this so neuron cannot react to another stimulus straight after the first action potential
• Ensures AP travels in one direction towards axon

Question 20

Relative Refractory Period

Answer 20

• Stage 4 of an AP
• Stops damage of ion gradients in neuron
• Another AP can be generated at this time but will have to be stronger to reach threshold

Question 21

Location of AP

Answer 21

• Generated in the axon initial segment (axon hillock) which has the lowest threshold (i.e. trigger zone for AP)
• Transmitted actively along the axon, away from the soma
• Dendrites are covered with synaptic ending form other neutrons receiving the synaptic currents

Question 22

RULE 2

Answer 22

When current generated by an outside source flows through the cell membrane from the outside to the inside there will be hyper polarisation (MP more negative)

When current generated by an outside source flows through the cell membrane from the inside to the outside there will be depolarisation (MP more positive) initiating an AP

Question 23

Activation Gate

Answer 23

Voltage sensor that responds to small changes in RMP and opens allowing Na+ influx
- Middle of protein

Question 24

Inactivation Gate

Answer 24

Voltage sensor that responses to large changes in the membrane potential and shuts the Na+ channels when the inside of the cell becomes too positive
- On the inside of the cell

Question 25

Sub-Threshold Passive Spread of Current

Answer 25

1. Passive current spread inside and outside the axon 2. Local depolarisation (sub threshold depolarisation at one region of the membrane) 2. Depolarisation at adjacent parts of the membrane - Current quickly dissipates as it flows along the axon

Question 26

Action Potential Transmission in Unmyelinated Axons

Answer 26

1. Action Potential (big depolarisation can reach threshold) 2. Passive current spread 3. Depolarisation of adjacent parts of the membrane to threshold 4. Activation of voltage-gated Na+ channels 5. New full size AP generated on both sides of the initial AP

Question 27

Unmyelinated Axon

Answer 27

- around 1um in diameter - slow continuous transmission of AP (1/s) - Passive current flow between 2 adjacent points is fast but AP must be regenerated at every point on the membrane (SLOW) - Delay to reach threshold membrane potential

Question 28

Myelinated Axon

Answer 28

- Around 10um in diameter - Fast, saltatory transmission of AP - Myelin sheath formed by Glia cells (oligodendrocytes in CNS, Schwann cells in PNS) - Myelin increases the resistance to current - Myelination is discontinuous, interrupted at the Nodes of Ranvier (here current can flow and Voltage gated ion channels are expressed)

Question 29

Action Potential Transmission in Myelinated Axons

Answer 29

- Increases AP speed but increasing the efficiency of the passive speed - AP's do not need to be regenerated at every part of the axon membrane - only generated at the Nodes of Ranvier

Question 30

Generation of AP in Sensory Neurons

Answer 30

- When a stimulus acts on receptors it evokes a graded depolarisation in sensory endings known as the receptor potential - Non-selective cation channels are activated by stretch (MP will go b/w Na+ and K+) - Receptor potential spreads passively to trigger zone where AP is generated - AP moves toward CNS along axon - Information about the strength of the stimulus is coded in the amplitude of the receptor potential and frequency of AP

Question 31

Types of synaptic transmission

Answer 31

- Chemical synapses | - Electrical synapses

Question 32

Chemical synapses

Answer 32

- Most in the brain and between neutrons and muscle fibres - Depolarisation at the presynaptic terminal causes the release of a neurotransmitter which diffuses across the synaptic cleft and binds to receptors in the postsynaptic membrane - Specificity - Complexity (type, time course, strength, location) - Plasticity (change is synaptic structure and function)

Question 33

Neurotransmitters

Answer 33

Chemical messengers that have an effect on ion channels and lead to depolarisation or hyper polarisation of the postsynaptic membrane

Question 34

EPSP

Answer 34

Excitatory Postsynaptic Potentials - evoke depolarisations of the postsynaptic membrane - Move passively from dendrites to axon hillock - AP can be generated via summation - Via opening of channels selective of Na+, K+, Ca2+ - Glutamic acid (Glutamate) - major in brain - ACh

Question 35

IPSP

Answer 35

Inhibitory Postsynaptic Potentials - evoke hyperpolarisations of the postsynaptic membrane - Move passively from dendrites to axon hillock - Via the opening of K+ channels - Gamma-aminobutyric acid (GABA) - Glycine

Question 36

Neuromuscular Junction

Answer 36

- AP moves down axon depolarising it - Voltage gated Ca2+ channels open and Ca2+ (and Na+) rush into the cell - Triggers release of ACh from vesicles in the presynaptic membrane and into the synaptic cleft - ACh interacts with postsynaptic membrane opening non-selective ligand gated cation channels - Leads to depolarisation of the postsynaptic membrane (End Plate Potential EPP) - Produces AP which will travel along the muscle fibre

Question 37

Synaptic delay

Answer 37

- 0.5ms | - Time between the initial action potential from the presynaptic membrane to the AP in the post synaptic membrane

Question 38

Direct gating

Answer 38

Transmitter binds to the receptor/ion channel complex causing it to open - Very fast (<1ms) and short lasting (ms)

Question 39

Indirect Gating

Answer 39

- Transmitter binds to receptors (G-Protein Coupled) - metabotropic - Activates biochemical pathway which involves a G-Protein - Production of seconding messengers (cAMP) activating Protein Kinase - Protein kinases phosphorylate ion channels causing them to open or close - Slower in onset and long lasting (seconds to minutes)

Question 40

Small Molecule (Classical) Neurotransmitters

Answer 40

Usually fast and act directly on postsynaptic receptors - Amino acids (Glutamate, GABA, Glycine) - ACh - Biogenic amines (Dopamine DA, Norepinephrine NE, Serotonin 5-HT)

Question 41

Neuropeptides

Answer 41

Large molecule chemical messengers with metabotropic action on postsynaptic receptors or modulatory action on the effects of other neurotransmitters. - Slow and diffuse action - Enkephalin, Substance P, Neuropeptide Y

Question 42

Neurotransmitter Inactivation

Answer 42

1. Diffusion - Removed from synaptic cleft by diffusion 2. Enzymatic Degradation - ACh is degraded by acetylcholinesterase 3. Re-uptake - Most common - Uptake back into presynaptic membrane vesicles

Question 43

Factors Determining Synaptic Action

Answer 43

1. The type of neurotransmitter/neuromodulator 2. Type of neurotransmitter receptor expressed in the postsynaptic membrane - A neurotransmitter can have multiple effects 3. The amount of neurotransmitter receptor expressed in the post synaptic membrane - Synaptic plasticity - Long term depression (LTD) - Long term pronunciation (LTP)

Question 44

Glutamate

Answer 44

- Binds to: AMPA: directly gated ion channel NMDA: directly gated ion channel Kainate: directly gated ion channel Metabotropic Glutamate Receptor (2nd Messenger) - Response depends on the type of activated receptor - Too much Glutamate release leads to excessive activation of neutrons through NMDA and AMPA/Kainate receptors

Question 45

Excitotoxicity

Answer 45

- Large Ca2+ influx is associated with over activation of NMDA receptors and causes damage of neurons causing brain injury

Question 46

Spatial Summation

Answer 46

Additive effect produced by many EPSP's that have been generated at many different synapses on the same post synaptic neuron at the same time - E1 + E2

Question 47

Temporal Summation

Answer 47

Additive effect produced by many EPSP's that have been generated at the same synapse by a series of high frequency of action potentials on the presynaptic neuron - E1 + E1