Section 6: ET - Neurons Flashcards
Neurons / nerve cells
The building blocks and instruments of communication in the brain
Neurons - size
20 microns in diameter
Dendrites extend ~1mm from cell body
Axon can be 1-2mm, or quite long (half a meter)
Neurons - types of communication
Electrical signals (dendrites, cell body, axon) Chemical signals (synapses) In a cycle (electrical responses lead to release of a chemical / neurotransmitter, which leads to electrical signalling)
Neurons - synaptic vs action potentials
Synaptic potential is transmission of electrical signals in dendrites spread towards cell body
Cell body can respond with an action potential, which once triggered is towards axon terminals
Axon terminals AKA…
Synaptic boutons
Dendrites, cell body and axon
Dendrites can be seen as input stage of info
Cell body seen as computing part which makes a decision whether to respond to a synaptic input
If cell body responds with action potential, it will be transmitted and lead to release of neurotransmitters at axon terminals
Cells - RMP and excitability
Almost all cells in body have -ve RMP
Only neurons and muscle fibres can suddenly respond with a transient change of this potential (i.e. action potential) in response to a stimulus - so they are excitable
Methods of measuring intracellular potentials
Microelectrode recording technique
Patch-clamp technique
Measuring intracellular potentials - microelectrode recording technique
Glass capillary (tip < 1 micron, but still has small opening) attached to microelectrode (filled with electrolyte to conduct current), connected to a voltmeter, and second pole outside in extracellular space
Measuring intracellular potentials - microelectrode vs patch-clamp technique
Microelectrodes:
Records RMP, APs and synaptic potentials in neurons or their processes
Can also be used to depolarise or hyperpolarise neurons if a current passes through them
Patch-clamp technique:
Same as above, but also records overall current which flows through cell membrane or a single ion channel
Measuring intracellular potentials - patch-clamp technique - drawbacks
Must fill pipette with electrolytes, otherwise current won’t be transmitted
Forms large hole and changes composition of inside of cell
Resting Membrane Potential (RMP)
Electrical potential difference (50-70mV) across the cell membrane which results from separation of charge
RMP - inside and outside cell
By convention, the potential outside the cell is defined as ‘zero’
Intracellular potential is (normally) below zero
RMP is due to…
Unequal conc of Na+ and K+ inside and outside the cell
Unequal permeability of cell membrane to these ions
Electrogenic action of Na-K pump (only a small contribution)
Approximate conc of K+ and Na+ inside and outside neurons
Conc of K+ inside much higher than K+ outside (5mM outside, 100mM inside)
Conc of Na+ outside much higher than Na+ inside (150mM outside, 15mM inside)
Results in conc gradients
Permeability of cell membrane at rest
Much more permeable to K+ than to Na+
How are conc gradients for K+ and Na+ maintained
By Na+/K+ pump
3/2 ratio: 3 Na+ out, 2 K+ in
Types of ion channels (have selective permeability to ions) in neurons
Non-gated (leak) channels - open at rest Gated channels (voltage, ligand, or mechanically gated) - closed at rest
Neuron cell membranes - leak K+ and Na+ channels
Many leak K+ channels but very few leak Na+ channels
At rest:
P(K+) / P(Na+) ≈ 40/1
where P is membrane permeability
Equilibrium potential
An intracellular potential at which the net flow of ions is zero despite a conc gradient and permeability
Zero net flow
Since K+ ion leaves, environment becomes -ve –> electrostatic force causes movement of ions back into cell as -ve environment attracts +ve ions - net flow is zero
Nernst equation
Used to calculate equilibrium potential for each ion
E(ion) = 61.5mV x log[ion]o / [ion]i
Only applies when a cell membrane is permeable to only ONE ion (i.e. has leak channels only for one specific ion)
Nernst equation - K+ and Na+
E(K) = -80mV, i.e. at -80mV at equilibrium potential for K+, there's a steady state where there's no net flow, gradients are maintained and same no of ions that leave the cell will be attracted by the -ve potential inside the cell E(Na) = +60mV
Calculating membrane potential from equilibrium potential
Equilibrium potential can be used to calculate membrane potential, but only in cells where the cell membrane is permeable to K+
Glia cells - RMP
Have leak channels only for K+ (not Na+), so RMP for glia cells = E(K) = -80mV
Neurons - leak channels and RMP
RMP affected by K+ leak channels AND Na+ leak channels
Neurons - leak channels and RMP - rule
The higher the permeability of the cell membrane to a particular ion, the greater the ability of this ion to shift the RMP toward its equilibrium potential
i.e. membrane potential inside cell could be anywhere between -80 and +60, but where it is exactly depends on relative permeability for ions
Neurons - RMP at rest
At rest, membrane permeability in neurons is much higher to K+ than to Na+ so RMP is closer to equilibrium potential for K+ (E(K)) than for Na+ (E(Na))
RMP - neurons vs glia cells
In neurons, RMP is less -ve than E(K) (approx -65mV) due to a small contribution of leak Na+ channels
Goldman equation
Calculates value of RMP taking into account both conc gradients AND relative permeability of resting cell membrane to K+ and Na+ ions
V(m) = 61.5 log {Pk[K+]o + PNa[Na+]o} / {Pk[K+]i + PNa[Na+]i}
V(m) = -65mV
Potential inside neurons - constant?
Not constant - changes when ion conc changes or membrane permeability changes
Potential inside neurons - hyperpolarisation vs depolarisation
Hyperpolarisation:
Becomes more -ve
Potential inside cell moves closer to E(K) and away from E(Na)
Depolarisation:
Becomes less -ve
Potential inside cell moves away from E(K) and closer to E(Na)
Action potentials AKA
Spike
Nerve impulse
Discharge
What is an action potential (AP)
A brief fluctuation in MP caused by a transient opening of voltage-gated ion channels, which spreads like a wave along an axon
When do action potentials occur
After the membrane potential reaches a certain voltage called the threshold (~-55mV)
Why are APs significant
Info is coded in frequency of APs –> can be regarded as a form of language by which neurons communicate
A key element of signal transmission along axons
Stages of action potentials
- A slow and graded depolarisation evoked by a stimulus causes shift of MP from resting value to threshold
1. After membrane potential reaches threshold: fast depolarisation to ~+30mV (overshoot) for a short period of time
2. Process reverses direction and MP goes back down towards starting value - repolarisation
3. Becomes slightly more -ve than RMP before going back to RMP - after-hyperpolarisation (AHP)
Action potentials - refractory period
An important feature of nerve cells
A time during the action potential when the nerve cell isn’t excitable (i.e. after the first stimulus, it won’t evoke a second action potential during this period)
APs - absolute refractory period
Stages 1 and 2
Even if second stimulus is extremely powerful, won’t evoke an AP
APs - relative refractory period
If strong stimulus applied, may evoke another action potential
Harder for stimulus to reach threshold as MP is more -ve so has to increase by a higher amount
i.e. stronger stimulus needed to depolarise it to threshold
AP - stimuli
Can be…
Physical (electric current, light or mechanical stretch)
Chemical (drug or neurotransmitter)
Synaptic transmission caused by neurotransmitters can…
Depolarise cell membrane to threshold and evoke action potentials
What happens when MP reaches the threshold
There is a sudden activation/opening of voltage-gated Na+ channels
Extreme increased permeability to Na+
What are voltage-gated channels
Gated channels sensitive to voltage outside and become permeable when membrane depolarises
AP - opening of Na+ and K+ channels
Opening of voltage-gated Na+ channels are short lasting, as they quickly inactivate
P(K):P(Na) –> 1:20 –> MP shifts towards E(Na) –> overshoot
Followed by transient opening of voltage-gated K+ channels –> permeability to K+ becomes even higher –> repolarisation and AHP –> MP shifts towards E(K); P(K):P(Na) ≈ 100:1
When inactivated, goes back to RMP
Key role of voltage-gated Na+ channels in AP
When voltage threshold is reached, Na+ channels open and Na+ ions move into cell along both the conc and electrical gradient
Influx of Na+ slows down and stops when:
1. Inside potential becomes +ve (towards E(Na+)) and thus attracts Na+ ions less (electrostatic force decreases)
2. Na+ channels inactivate/close
Na+ channels: Activation gate
Residues which have a certain charge
Act as a voltage sensor and detect small changes in MP and change configuration
If there’s depolarisation that reaches threshold, activation gate opens –> Na+ diffuses from outside to inside of cell along their conc gradient
AP - stage 1 speed
Fast as there are 2 factors causing Na+ to move into cell
Conc gradient and -vely charged interior of cell
Why do nerve cells try to avoid a large influx of Na+
It would depolarise the cell –> loses MP potential
So, APs are short-lasting mainly because Na+ channels activate, but v quickly inactivate
Na+ channels: Inactivation gate
Sense depolarisation and changes conformation to block channel
Closes before activation gate closes (before MP reaches E(Na), usually stops at +30mV); double mechanism to prevent cell from getting too much Na+
