Neuroscience Flashcards
What is neuroscience?
A scientific discipline of the functions of the brain
What are we covering?
Neuron structure
The Resting membrane potential
Action potentials
Synaptic communication
Communication is achieved by…
Electrical signals (Dendrites, cell body, axon) Chemical signals (synapses)
Nobel prize winners 1963
Hodgkin & Huxley (1938) Giant Squid’s axon
What is the resting membrane potential?
-50 - -70mV
What is an action potential?
When the charge rises to about 50 mV
Almost all cells have a negative resting potential but which are excitable?
Neurons, muscle fibres and endocrine cells
How are the intracellular potentials measured today?
- The microelectrode technique
2. The patch-clamp technique
What is created by the patch-clamp technique?
The Gigaohm seal (the ability to record the flow of currents)
What is the RMP?
Electrical potential difference ( - 50 - -70) across the cell membrane which results from separation of charge.
What is the RMP due to?
1.Unequal concentrations of Na+ and K+ inside and outside the cell
2.Unequal permeability of the cell membrane to these ions.
[3. Electrogenic action of the Na-K pump]
Concentrations outside the cell…
K+ 5 mM
Na+ 150 mM
Cl- 150 mM
Concentrations inside the cell…
K+ 100 mM
Na+ 15 mM
Cl- 13 mM
Do calcium ions affect the RMP?
No
Do negative charged proteins inside the cell affect the RMP?
No because the membrane is not permeable for them.
How are the Na+ K+ concentrations maintained?
The Na / K ATPase Pump
What are the amounts of Na and K in one pump action?
3 Na and 2 K
How is the unequal permeability of the cell membrane to different ions explained?
1 . Non-gated (leak) channels
2. Gated channels (voltage-gated, ligand-gated, mechanically gated)
The channels are selectively permeable.
How many non-gated ion channels are there?
Many for K Very few for Na PK+/PNa+ 40/1 Permeability ration
How does unequal concentration and permeability result in negative RMP?
Equilibrium potential
An intracellular potential at which the net flow of ions is zero, in spite of the concentration gradient and permeability.
How do we calculate the equilibrium potential for each ion?
The Nernst equation
E(ion) = 61.5 m V x log [ion]outside / [ion]inside
Eg. K = 61.5 mV x log 5 / 100 = 61.5 mV x (-1.3) = -80 mv
Which cells have a membrane potential of -80 mV
Glial cells
What are the equilibriium potentials for K, Na and Cl?
Ek = -80 mV ENa = + 60mV ECl = -65 mV
The Nernst equation only applies when
When a cell has only one type of ion channel is present in the membrane.
What is the rule for permeability and equilibrium potential?
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.
Which are more negative, neurons or glial cells?
Glial cells because they only have K+ channels, whereas neurons have Na+ channels which skew this.
The Goldman Equation is…?
A way of calculating the value of the RMP taking into account both the concentration gradients and the relative permeability of the resting membrane to K+ and Na+ ions.
What is an action potential?
A brief fluctuation in membrane potential caused by a transient opening of voltage-gate channels, which spreads like a wave along the axon.
What is the threshold of an action potential?
-55 mV
What is the major significance of APs?
It is the frequency of the APs which sends information
What are the names of the refractory periods in an AP?
Absolute (Fast depolarisation, replorisataion)
Relative (After threshold regained and AHP)
The stimulus that triggers an AP can be either:
Physical (electric or mechanical)
Chemical
What causes the fast depolarisation?
Opening of voltage gates Na+ channels
During fast polarisation what is the K+:Na+ ratio?
1:20
During repolarisation what is the K+/Na+ ratio?
100:1
How is the Na+ voltage gate closed once the MP reaches 0?
There is an inactivation gate (ball and chain)
What are the two gates of Na+ channels?
Activation gate (opens at -55mV) Inactivation gate (Closes at opens at below -55 MV)
If a current is generated from the outside will it hyperpolrasie or depolarise?
Hyperpolarise (and vice versa)
How are APs generated physiologically?
They are triggered at the ‘initial segment’ (by Axon hillock) where they are evoked by Excitatory postsynaptic potentials EPSPs.
What are the two types of axon?
Myelinated and Non-myelinated
What are the two stages of action potential transmission?
- Passive spread
2. Active Spread
What are the two main structures of the axon?
Axolemma and Axoplasm
How far does passive spreading reach?
about 1 mm
What is the speed of AP in a non-myelinated axon?
1m/sec
What is the speed of AP in a myelinated axon?
20 - 100 m/sec
What cells give rise to myelin sheath in the CNS?
Oligodendrocytes
What cells give rise to myelin sheath in the PNS?
Schwann Cells
What is saltatory conduction?
The passive spread of an AP to each node of Ranvier
What stops the AP going backwards?
The absolute refractory period
What is the orthodromic direction?
The direction of an AP from the cell body to the synapses
What is antidromic direction?
The direction of an AP towards the cell body
What would happen if two APs were going in opposite directions towards each other?
They would collide and cancel each other
How are APs generated in the sensory neurons?
Through mechanical stretching?
What is different about the stretching of a PNS neuron to a CNS neuron?
When stretched an AP is not immediately generated.
First it evokes a graded depolarisation known as the receptor potential.
The receptor potential spreads passively to the trigger zone where voltage-gated sodium channels open and AP occurs.
What is an axon to dendrite connection called?
axo-dendritic connection
What is a an axon to muscle junction called?
A motoneuon connection
Stages of a neuromuscular excitatory transmission…
- Increased presynaptic permeability of Ca2+
- Vesicles fuse with presynaptic membrane
- Release of neurotransmitter by exocytosis
- Reaction of of transmitters with postsynaptic recptors
- Activation of synaptic channels
- Postsynaptic action potential
How long does a synaptic transmission take in neuromuscular junctions?
Roughly .5 ms
What is the main neurotransmitter of neuromuscular transmission?
Acetylcholine
What ions cause the postsynaptic action potential?
Na+ and K+
(Permeability increases for both)
Non-selective cation channel
Do neuromuscular junctions always cause an AP?
Yes they are always suprathreshold
What are the two main categories of synapses in the CNS?
Excitatory (depolarising)
Inhibiting (hyperpolarising)
What is the typical neurotransmitters in EPSP and their functions?
Glutamic acid or Acetylcholine
Transient opening of Na+, K+, Ca2+ channels
What are the typical neurotransmitters and functions of IPSPs?
Mainly GABA - or - glycine
Transient opening of K+ - or - Cl- Channels
What happens when glycine ( or GABA b) opens postsynaptic Cl- channels?
If it is at -65 mV there is no hyperpolarisation
(it is already at equilibrium, there is an affect if it is above - 65mV)
It is still inhibitory however, because it increase resistance to charge.
What are the classifications of neurotransmitters?
Chemical structure:
- Small molecule neurotransmitters (‘Classical’ neurotranmitters)
- Neuropeptides (Neuromodulators)
What is the main types of small molecule neurotransmitters?
Fast action
Direct
- Amino acids - (Glutamte, GABA, Glycine)
- Acetylcholine
- Amines (Dopamine, noradrenaline, serotonin)
- ATP
What are the main characteristics of Neuropeptides?
Large molecule chemicals that have an indirect action (metabotropic) or modulatory action in the effects of other neurotranmitters
- Putative neurotransmitters
- Slow
- More diffuse (volume transmission)
- Neuropeptide Y (NPY)
- Substance P
- Kisspeptin
- Endorphins
What determines the type of synaptic action?
- Type of neurotransmitter/ neuromodulater
- Type of neurotransmitter receptor
What types of channels do glutamate activate in the synaptic cleft?
- Metabotropic glutamate
- AMPA
- NMDA
- Kainate
What happens when NMDA when it is activated?
It is permeable to multiple ions including Ca+
What happens when too much glutamate release?
Excessive depolarisation and over activation. Long term opening of NMDA receptors causes excessive Ca2+ entry, leading to damage of the neuron - excitotoxicity
What is excitotoxicity?
The over activation of NMDA receptors leading to excess Ca2+ in the cell, leading to neuron damage.
How does neurotransmission inactivate?
-Diffusion
-Enzymatic degradation
-Re-uptake (for most aminoacids and amines)
(Involves neurotranmitter transporters in presynaptic membrane or adjacent glial cells e.g. glutamate transporter)
How large is each postsynaptic potential?
about .1 mV
(Potentials decay when they are passively conducted from dendrites) i.e. can change from 10 mV to .1 mV from dendrite to axon initial segment
What are the two types of summation in neurotransmission?
Temporal and spatial
