neuronal communication

Question 1

Explain potential difference and excitable cells

Answer 1

excitable cells - have potential difference/voltage over cell membrane
- have resting membrane potential
– can be electrically excited to fire action potentials (all-or-none voltage pulses) above some threshold
Eg of excitable cells: neurones, cardiac myocytes, and skeletal muscle

Potential (voltage) difference (PD) across membrane of excitable cells

PD across a membrane arises by:
- passive movement of ions
Permeability of membrane
Driving voltage, down electrochemical gradients(no energy used)
- Active transport of ions
Against conc/electrical gradient
Required metabolic energy

Question 2

charge, voltage, current, conductance, capacitance

Question 3

define: membrane potential, resting MP, depolarisation, hyperpolarisation

Answer 3

Membrane potential or Vm : voltage difference across cell membrane (intracellular – extracellular V)

Resting Membrane Potential (RMP): steady-state membrane potential when there are no electrical inputs to a cell, generated by its own intrinsic electrical properties

Depolarisation: positive change in membrane potential (towards zero)

Hyperpolarisation: negative change in membrane potential (away from zero)

Question 4

Describe the permeability of a plasma membrane of a typical excitable cell.

Answer 4

What can get through cell membrane?
Depends on molecule size, electrical charge, molecular shape, solubility, etc.
Membranes differ in permeabilities:
Depend on lipids and proteins present and their arrangement;
lipid impermeable to ions
Cell membranes in their resting state:
Fairly readily permeable to K+ and less to Cl- (via ion channels) Poorly permeable to Na+
Impermeable to various large organic anions formed in cells

how does charge move/change and go through the membrane:
Specialised trans-membrane proteins:
* Ion channels:
* mechanism directly affecting membrane potential (‘passive’ flow of ions down their net concentration and electrical gradients)
* Ion pumps and transporters
Expend metabolic energy to move ions up (against) their concentration and electrical gradients
Set up concentration gradients utilised by ion channels:
energise’ the membrane (store energy in concn gradients)

Question 5

State typical intracellular and extracellular concentrations of K+, Na+ and Cl-.

Answer 5

Na+ and K+ and other ions (hydrophilic) cannot pass directly through the lipid bilayer membrane (hydrophobic)

They can cross the membrane via ion channel proteins

in the cell:
K+ 140
Na+ 15
Cl- 7

out of the cell:
K+ 4
Na+ 150
Cl- 125

Question 6

reasons for unequal concentrations(of ions)

Answer 6

Large organic anions produced by cell that cannot cross membrane
Active transport mechanism that expend metabolic energy
(e.g. the Na+/K+ ATPase pump actively transports Na+ out of the cell and K+ into the cell, powered by ATP hydrolysis)
Kidneys and other organs regulate extracellular concentrations homeostatically

Question 7

 Explain the concept of electro-chemical equilibrium.

Answer 7

mix of an electrical gradient from charges/potential differences and a concentration gradient from volume of ions in an area

Question 8

 Use the Nernst equation to calculate equilibrium potentials.

Answer 8

Ex = - RT/zxF ln [X]i/[X]o

at 37 d.cel.
Ex = 60log10 [x]o/[x]i

x = specific ion
Ex = Equilibrium potential for ion x
R = universal gas constant
T = temperature (in degrees absolute)
z = the valence of the ion
(e.g. +1 for K+; -1 for Cl-)
F = faraday’s constant
[x]o = concentration of X outside
[x]i = concentration of X inside

Question 9

Use fractional conductance-weighted sum of equilibrium potentials to calculate RMP.

Answer 9

to calculate RMP
Vm = Fk Ek + fcat Ecat

Where Fk and fcat are the fractional permeabilities of the different channels

Question 10

Describe the origin of the resting membrane potential (RMP).

Answer 10

Two fundamental properties of cells give rise to the existence of a resting membrane potential:
1. Unequal distribution of ions across membrane (maintained by Na+/K+ pump)
2. Selective permeability of the cell membrane (PK&raquo_space; PNa)

Question 11

Describe the responses of an excitable cell to depolarisation.

Question 12

action potential

Answer 12

action potential (AP) - a digital-like voltage pulse with a biological action (transient positive change in membrane potential).
* Changes in membrane potential determine if an action potential will occur or not (“all or none”).
* AP triggered positive to a threshold membrane potential.
* Excitatory neurotransmitters cause small positive changes in membrane potential; these excitatory postsynaptic potentials (EPSPs) ‘summate’ (add up) and can trigger an action potential.
* Inhibitory neurotransmitters cause inhibitory (negative-going) postsynaptic potentials (IPSPs) which can prevent action potentials firing.
* Action potentials are required for correct functioning of the brain, heart and skeletal muscles and many other types of cell.

Question 13

Describe the function of afferent and efferent neurons.

Answer 13

afferent neurone- sensory neurone that takes the sense from the receptor to the spinal cord/CNS
efferent neurone- motor neurone that takes the information from the CNS to the effector organ (muscle/gland)

Question 14

synapse and synaptic transmission.

Answer 14

Synapse = the small gap that exists between a pre and post synaptic membrane

*Excitatory synapses – electrical activity in presynaptic neurone to increase the excitability of postsynaptic neurone [inhibitory synapses - ……. “decreases”……..]
Two types of synapses:
1. Chemical synapses - prevent direct electrical propagation of AP from pre- to post-synaptic neuron
2. Electrical synapses - exist but rare in CNS

chemical synaptic transmission:
Synaptic delay ~ 0.5 ms
Synapse is 20 – 30 nm
Removal:
* enzymes
* reuptake
* uptake by glial cells

Question 15

Describe cellular pathways involved in vesicle release.

Answer 15

FPMs = fusion protein macromolecules
1. Opening of Ca2+ channels and actin.
2. FPM separate to allow fusion.
3. Vesicle membrane incorporated into presynaptic membrane.
4. Clathrin molecules assist inward movement of the vesicle membrane.
Dynamic assists in FPM pairs and pinching the neck of the emerging vesicle.
5. Vesicle is now free for recycling.

Question 16

removing neurotransmitters from the synaptic cleft. and novichok poisoning

Answer 16

Three key mechanisms by which neurotransmitters are removed from the synaptic cleft:
1. Enzymatic breakdown.
2. Active reuptake (rapid).
* pumped back into pre-synaptic terminal
3. Active uptake (rapid).
* pumped into glial cells

novichok poisoning:
A group of nerve agents
*Inhibits acetylcholinesterase
*Spasm / prevents relaxation of muscles (cardiac and respiratory)
*Cause of death asphyxiation or cardiac arrest.
*Fast acting

Question 17

Describe the ionic basis of excitatory postsynaptic potential (EPSPs) and inhibitory postsynaptic potential (IPSPs).

Answer 17

EPSP = Excitatory post-synaptic potential
IPSP = Inhibitory post-synaptic potential

A bit like “mini action potentials” which cause a small transient change in membrane potential of a cell.
They can summate (an opposed to A.P.s)

EPSPs can lead to action potential firing - if it reaches threshold potential

Question 18

Explain temporal and spatial summation.

Answer 18

Summation of postsynaptic potentials occurs when a presynaptic neuron fires repeatedly at a high rate (“temporal summation”)
or when several presynaptic terminals fire at the same time (“spatial summation”) or from a combination of temporal and spatial summation

Question 19

Define convergence and divergence and state their significance in synaptic physiology.

Answer 19

convergence enables integrating information from a number of inputs

divergence allows the responce to be felt by a number of effectors

Question 20

Describe pre-synaptic inhibition.

Answer 20

inhibition before the synapse occurs

Question 21

Outline the principles of intracellular and patch (including whole-cell) recording.

Answer 21

Intracellular recording – recording electrical activity across a membrane of one single cell (one electrode is inside the cell and one (earth) is outside).
Extracellular recording – recording electrical activity from a population of cells (both electrodes are outside of the cell).

Intracellular (sharp electrode) recording with an electrolyte-filled hollow glass ‘spear’ (< 0.1 μm tip)
Patch recording (with a clean ~ 1+ μm tip diameter glass pipette)

Record from slices of brain tissue, kept alive in solution that mimics extracellular fluid (cerebrospinal fluid, CSF) or record from cultured, dissociated cells
Measure voltage or current in the cell
Record action potentials / synaptic
communication using electrodes.
Ca2+ imaging using a dye

intracellular:
In vivo (intact animals, via skull ‘window’) Measure electrically during behaviour

patch:
* “Giga-seal” > 109 Ω
* Ensures negligible current leaks out under rim of pipette
* Reduces the noise
* Enables the detection of very small currents (picoamps, 10-12 A, pA) flowing through single channels

Question 22

neurones and capacitance

Answer 22

Lipid membranes have capacitance this means:
The lipid membrane separates (stores) opposite electric charges
Voltage (potential) is produced across the membrane between separated opposite charges, by electrostatic attraction

Charge and Voltage are different:
Charge = current x time
Voltage = charge stored/capacitance
(ability of the membrane to store charge)

Question 23

Compare action potential propagation in unmyelinated and myelinated axons.

Answer 23

Conduction velocity = the speed at which propagation of the action potential occurs.
- Measured in metres / second (m/s)
- Can be as fast at 100m/s or as slow as 1m/s

Node of Ranvier: gaps in myelin sheath high density of Na+ channels

AP propogation in a myelinated fibre:
Saltatory conduction (from the Latin for leap) propagation of AP along the axon from one node to the next, increasing the conduction velocity.

Nodes occur at intervals of 0.2 – 2 mm along the axon.
Action potentials propagate quickly in myelinated nerves – up to 100m/s. The current world record for men’s 100m is Usain Bolt at 9.58 seconds

Question 24

State the factors that affect conduction velocity and explain underlying mechanisms.

Answer 24

• Myelination of the axon
  – Good insulator
  – Increases resistance (R)
  – Decreases conductance (G)
• Diameter of the axon
  – Internal resistance

Question 25

Outline the principles of extracellular recording.

Answer 25

• Extracellular electrodes record from population of neurons
• Measure voltage difference between two electrodes relative to one other
• Stimulate whole nerve
• Biphasic compound action potential

Question 26

 Describe compound action potentials.

Answer 26

graded phenomenon:
* AP recorded from single fibre is “all or none”.
* Compound AP recorded from whole nerve is NOT
“all or none” they are graded.
* Graded dependent on size of the stimulus.
* Small stim – few fibres – small potential
* Larger stimulus – more fibres – larger potential
* Maximum stimulus – all fibres – max potential