Neurons Flashcards
Neurons
Building blocks and instrument of communication in brain
Synaptic potential
Inputs from other neurons from dendritic tree to cell body ‘soma’
Action potential
Signal flows away from soma to synaptic boutons (axon terminal), communicate with other neurons
Neurons consist of
Soma (cell body), Dendrites, usually 1 axon
Purkinje cell
Found in cerebellum
Cerebellum
- Receives infro from sensory systems, spinal cord, other parts of brain
- Coordinates voluntary responses,
Pyramidal cell
Found in cerebral cortex
Cerebral cortex
Outer layer of cerebrum
Important role in consciousness, thinking, action
Resting Membrane Potential (RMP)
- Electrical potential difference across cell membrane which results form separation of charge
- Absence of synaptic and action potentials
(-50 -> -70 mV) - Cytoplasm more negative than extracellular space
How and what parts of the body are excitable
Neurons, muscle fibres, some endocrine cells
Respond with short-term change of potential by Action Potential, in response to a stimulus
What causes RMP
Unequal conc. of Na+ and K+ inside and outside cell
Unequal permeability of cell membrane to these ions
Small contribution:
Electrogenic action of Na-K pump
Unequal conc. of Na+ and K+
Carrier protein, Na-K pump, ‘salty banana’
3 Na OUT, 2 K IN
Primary active transport
ATP needed]
Explaining unequal permeability
Selective permeability of ions: non-gated 'leak' channels - 40:1 ratio, K to Na - Open @ rest
Gated (voltage, ligand) channels
- Closed @ rest
Equilibrium potential of Na and K
K outside = 5 mM
Na inside = 15 mM
K inside = 100 mm
Na outside = 150mM
Nernst equation for each ion at equilibrium potential
61.5 x log( [Ion] outside/ [ion] inside)
E(K) = -80 mV E(Na) = + 60 mV
Only applies if cell membrane permeable to ONLY ONE ION
RMP rule
Higher permeability of cell membrane to particular ion (e.g. K+), RMP closer to equilibrium for that ion, (e.g. E(K+)) = -80 mV
- closer to -80 mV than to E(Na+) which is +30 mV
Goldman Equation
Calculates RMP taking into account:
- Both concentration gradients
- Relative permeability of cell membrane to K+ and Na+ ions
Action Potential
Brief fluctuation in membrane potential caused by transient opening of voltage-gated ion channels (mainly Na+ and K+) that spread like a wave along neuron
- Occurs after threshold of -55 mV reached
- Can also be transmitted along muscle fibres
Significance of Action Potentials
Information is coded in the frequency of action potentials
- AP’s regarded as ‘language’ which neurons communicate by
Key element of signal transmissions along axons (often v. long)
First stage of AP
Fast depolarisation - After threshold of -55mV reached - Overshoot from -55mV to +30 mV - Voltage-gated Na+ channels open very fast P(Na+) > P(K+) in a 20:1 ratio
Stimulus
Detectable change in internal/external environment
- Physical
(light, electric current, stretch) - Chemical
(drug, synaptic excitation)
2nd stage of AP
Repolarisation
- Na+ channels inactivate, and are short lived
- Transient opening of K+ channels repolarise membrane potential
- P(K+) > P(Na+) in a 100:1 ratio
Why doesn’t membrane potential reach +60 mV @ 1st stage
MP shifts towards E(Na+) as Na: K ratio is 20:1
- Na+ channels short lived and quickly inactivate
- Transient opening of K+ voltage-gated channels
Leads to repolarisation and AHP
MP shifts towards E (K+) which is -80mV as P(K+) > P(Na+) 100:1
3rd stage of AP
After Hyperpolarisation (AHP)
Voltage-gated K+ channels open for a while then close
- Dips belows -70mV (RMP) as it wants to get closer to E(K+) which is -80mV
- P(K+) > P(Na+)
Hyperpolarisation
If Membrane potential becomes MORE negative
(e.g. -70mV to -75mV)
Potential inside cell moves closer to E(K+) and away from E(Na+)
Results from slow closing of voltage gated K+ channels
Depolarisation
If Membrane potential becomes LESS negative
(e.g. -70mV to -60mV)
Potential inside cell moves closer to E(Na+) and away from E(K+)
Are Neuron potentials constant
NO
Change when conc. of ions or membrane permeability change
Activation/ Deactivation of Na+ channel
1) RMP (negative MP) Voltage sensor/ ACTIVATION GATE opens when it senses depolarisation
2) Depolarisation to threshold (less negative MP)
3) Fraction of a millisecond later inactivation occurs by INACTIVATION GATE
(+ MP)
4) Back to initial state when membrane repolarises
activation gate back, inactivation gate released
SUPRAthreshold
Stimulus large enough in magnitude to produce an AP in excitable cells
How can AP evoked (awaken)
1) Outside from + to - (extracellular fluid) - electrolytes etc.
2) Across membrane and inside axon
ONLY path 2) can change RMP
Current generated by OUTSIDE source flows through cell membrane from OUTSIDE -> INSIDE
(Hyperpolarisation- more -ve)
INSIDE -> OUTSIDE
Depolarisation (MP less -ve)
Which way does current flow
Current flow is shown by direction/ movement of cations
How are AP’s first generated in CNS neurons
AP’s first generated in axon initial segment (axon hillock) which has the lowest threshold so acts as a ‘trigger zone’ for AP’s
How does depolarisation occur in CNS neurons
Caused by excitatory postsynaptic potentials (EPSP’s), spread passively from dendrites to axon initial segment
Once AP generated, it is transmitted ACTIVELY along axon, away from soma
Chemical potential
Difference in solute concentrations across a membrane
Electrical potential
Difference in charge across a membrane
Electrochemical gradient
Sum of chemical and electrical gradients for that particular ion
How does repolarisation of membrane potential occur during action potential of a neuron?
K+ efflux (leaves cell)
as Na+ channels are closed so can’t enter or leave
Where are action potentials regenerated as they propagate along a myelinated axon?
At nodes
Voltage-gated sodium channels are largely restricted to the nodes between myelinated internodes.
Myelinated axons
Larger diameter than unmyelinated (5-10 um)
AP’s transmission is fast and
saltatory (large steps)
20 to 100 m/sec
Which type of axon will velocity of action potential conduction be the fastest?
Myelinated axons with the largest diameter
What changes occur to voltage-gated Na+ and K+ channels at the peak of depolarization?
Inactivation gates of voltage-gated Na+ channels close, while activation gates of voltage-gated K+ channels open.
Unmyelinated axons
Small diameter (1 um) AP transmission must be REGENERATED at EVERY POINT on membrane therefore is conduction velocity is slow and continuous
1 m/sec
Action potential transmitted in unmyelinated axons
“battery”
1) Action potential
2) Passive current flow
3) Depolarisation of ADJACENT parts of membrane to threshold
4) Voltage-gated Na+ channels in adjacent parts of membrane open
5) New FULL SIZE AP generated in adjacent parts of membrane
AP transmission of myelinated axons
Increase efficiency of passive thread
Only regenerated @ NODES OF RANVIER
Current flows passively between nodes ‘saltatory conduction’
What is the Myelin Sheath formed from
Formed by two types of glia cells
Oligodendrocytes in CNS
Schwann cells in PNS
Myelin
‘Insulates’ axon, NO AP generated here, as no flow of current
LESS current dissipation along axon
Under physiological conditions why does AP only flow in one direction
Due to absolute refractory period (nerve cell can’t respond to another stimulus)
Na+ channels still INACTIVATED
By the time ARP is over, AP has already moved down axon towards next NoR
How long does absolute refractory period last
1-2 ms
Occurs during stage 1+2 of AP
Why don’t we have all myelinated axons in our body
Although they transmit AP faster, they are larger in size, so we would fit less axons into smaller spaces (e.g. skull)
Receptor Potential concept
When stimulus acts on receptors in SENSORY neurons, AP’s are not immediate
1) Graded depolarisation (aka receptor potential) at sensory endings
Receptor potential PASSIVELY spreads to TRIGGER ZONE
Trigger Zone
Where AP’s are generated in sensory neurons
Contains Na+ and K+ voltage gated channels for depolarisation
Sensory Neurons
Unipolar
Can be myelinated or non-myelinated
AP’s travel towards CNS
Muscle spindles
Gated channels by mechanical force
Stretch of membrane opens channel
Non-selective cation channels, Na+ moves in more than K+ wants to leave
Stretch of stimulus on sensory muscle spindle
Coded by amplitude of receptor potential and frequency of AP’s
Most abundant class of neuron in the central nervous system is
Multipolar
Branches along axons
Collaterals
Extensive damage to oligodendrocytes in CNS can cause
Loss of sensation and motor control
Synaptic transmission
Process of transferring information between neurons or between neuron and muscle fibres
Two ways synaptic transmission occurs between neurons
1) Chemical synapses
2) Electrical synapses (via pores called ‘gap junctions’)
Where do Chemical Synapses occur
Between
- Neurons in brain
- Neurons and muscle fibres
Neuromuscular junction
AKA ‘end plate’
Synapse between neuron and muscle fibre
Two main types of chemical Synapses
Excitatory Synapse
Inhibitory Synapse
Excitatory Synapses
EPSP
Depolarisation of Post synaptic neuron
Excitatory Postsynaptic Potential
Mechanism and Neurotransmitters of Excitatory synapses
Transient opening of channels selective for Na+, K+ and Ca2+
Glutamic acid (glutamate) Ach
Mechanism and Neurotransmitters of Inhibitory synapses
Transient opening of K+ channels
GABA (gamma-aminobutyric acid)
Glycine
Inhibitory Synapse
IPSP
Hyperpolarisation (more -ve, further away from threshold) of postsynaptic membrane
Increase in cell membrane permeability to K+
What are Neurotransmitters
Chemical ‘messengers’ that open (sometimes close) ion channels
Lead to depolarisation or hyperpolarisation
Each neurotransmitter can bind to many different receptors each have different neuron function
Small Molecule (Classical) Neurotransmitters and examples
Fast action (milliseconds) Directly act on postsynaptic membrane
Examples:
Amino acids
(glutamate, GABA, glycine)
Acetylcholine
Noradrenaline, Dopamine, serotonin
Neuropeptides (neuromodulators)
Large molecule Slow (sec -> minutes) Indirectly act on PSM Modulatory action - no effects themselves, but alter other neurotransmitter effects
Examples: Enkephalin Substance P Neuropeptide Y (NPY) Kisspeptin
Factors determining synaptic action
Type of neurotransmitter
Type of receptor/ channel in PSM
Amount of neurotransmitter receptor present
Glutamate receptors and function in CNS
4 receptors in PSM, all allow Na+, K+ in
TOO much–> excessive activation of neurons
AMPA
NMDA (also allows Ca2+)
Kainate
‘metabotropic’ glutamate receptor (slower action)
Excitotoxicity
Excess Ca2+ from NMDA Neuron damage leading to - Stroke - Brain damage - Epilepsy
Synaptic Plasticity
ability of synapses to strengthen/weaken over time, in response to increases or decreases in their activity
LTP - long-term potentiation
LTD- long-term depression
How we learn, study, memorsie
Direct gating
Neurotransmitter directly binds to receptor/ ion channel
Depolarisation or hyperpolarisation of membrane as ions flow in
Fast (< 1 msec)
Short (msec range)
Indirect gating
Transmitter binds to G-coupled ‘metabotropic’ receptors activating a pathway involving G-proteins
Protein kinases activated by second messengers phosphorylate ion channels to open/close
- change MP
slow and long-lasting (sec-min)
Spatial summation
involves multiple AP on pre-SN that are active simultaneously
EPSP’s arrive at several places on neuron causing build up of depolarisation
EPSPs and IPSPs are integrated at the
Axon hillock
Temporal summation
When EPSPs arrive in rapid succession on ONE presynaptic neuron causing buildup of depolarization
More frequency of AP, higher chance total may exceed threshold
1st way of neurotransmitter inactivation
1) diffusion
- all NT removed from synaptic cleft to some degree by diffusion
2nd way of NT inactivation
2) Enzymatic degradation
- Ach removed by Achsterase (< 1ms)
Monoamine Oxidase (MAO) degrades amines
Peptidases cleave neuropeptides
3rd way of inactivation
3) Re-uptake
Specific neurotransmitter transporters in presynaptic membrane or adjacent glia cells
E.g. glutamate transporter takes gluatamate to different places
End plate potentials
Ionic channels to both Na+ and K+ (non-selective cationic channels)
