Neuronal function Flashcards
How does electrical signalling work?
The nervous system transmits information within individual nerve cells as rapidly changing voltages across the plasma membrane
What is the symbol and unit of charge?
Symbol = Q Coloumbs = unit
What is Faraday’s constant?
10^5 C = 1 mol monovalent ion
Define current. What is its symbol and and unit?
Current is the flow of charge
Symbol = I, unit = Amps (A)
What is voltage?
The field strength generated by charge separation where potential difference (p.d) is the difference in field strength between two points in space (unit = volts (V))
What will low resistance result in?
High conductance and high current for a given voltage
What are the symbols and units of conductance and resistance?
conductance g, conductance siemens
resistance R, ohms
R = 1/g
What is ohms law?
V=I*R
V=I/g
What is a capacitor, and what acts as a capacitor in the neuron?
Capacitor = 2 conductors separated by an insulator
in the neuron this is the membrane
What effect do capacitors have on circuits?
‘store’ charge causing a voltage to develop across it until voltage on capacitor = applied voltage where charge stored for given V depends on capacitance:
V*C=Q (Q = charge)
What is passive conduction?
- Response amplitude proportional to different stimulus strength
- attenuates (decreases over length of axon)
What is active conduction?
- Constant amplitude with frequency proportional to strength
- No attenuation
- Propagates with finite conduction
What are the advantages of active conduction?
- Resistant to noise
- Can travel a long distance with no degradation
What are the disadvantages of active conduction?
- Indirect coding so requires time to integrate
- Limited frequency range, as if frequency is too low will take too long to integrate
- “range fractionation” must be used to correct this
How doesw integration occur?
- Inputs at dendrites are non spiking
- Integrated over soma which if abpve threshold can cause spike at the axon hillock
What are the two types of summation?
Spatial (across different points)
Temporal (adds sum of close spikes, or pairing with inhibitory input)
What is the resistor-capacitor (RC) model?
- Phospholipid bi-layer (capacitor)
- Ion channels (resistor/conductor)
IN PARALLEL
What determines the final voltage at the point of injection in passive conduction?
How much current is being injected and the sum of the resistance (Ohms law) (V=IR)
Why does passive conduction voltage attenuate?
- Current moves along membrane and gradually leaks out via ion channels causing a voltage
- Gradually less current and voltage (in an exponential fashion)
What is the space length constant (λ)
Describes the how rapidly the voltage drops with distance
Voltage at point x = V max e^(-x/λ)
If λ is large voltage will drop slowly visa versa. The distance at which the voltage is around 37% of that of the point of current injection
What does λ depend on?
- membrane resistance (if low, current will leak out more quickly)
- internal resistance (if low current can spread more quickly)
- Glial wrapping (increase)
- Fatter axons (increase)
What does λ result in?
More integration
Why is there a delay in voltage response relative to current stimulus?
- Because the phospho-lipid membrane is a resistor
- Time taken to reach half of its final voltage is the time constant (t) where t = R*C
What does a longer time constant result in?
More potential for temporal integration
What are the limitations of the space constant equations?
- Assume infinitely long cable of constant diameter (not true for any neuron)
- Can’t calculate voltage profile
- Can use computer to stimulate this through “compartmental modelling”
What is the Nernst equation?
E (eq) = 58/z log (X outside/X inside)
What does the Nernst equation determine?
The equilibrium potential = voltage at which ions would be exactly balanced across the membrane
What is the equation for ion flux?
I = g (Em - Eeq) gives driving force V
What is the resting membrane potential?
NOT equilibrium potential ~-60mV. Is a compromise between the K and Na equilibrium potentials, although membrane more permeable to K so more weighted towards that
What are leakage channels?
- mediate the resting potential
- low conductance (higher for K) that is unchanging (unaffected by voltage and ligands)
What channels are responsible for action potentials?
- Voltage dependent Na/K channels
- Open (high conductance) when membrane depolarises
What is the difference in opening and shutting speeds between Na and K v-dependent channels?
- Na open rapidly and shut automatically even if membrane is still depolarised
- K open and shut slowly
What is the absolute refractory period caused by?
- Na channels take time to de-inactive until then cannot open
What is the relative refractory period caused by?
- K channels shut slowly causing excess K conductance, harder to cause spike (but still possible)
Why are action potentials hard to investigate?
Action potentials involve change in voltage, but these change conductance and current. Cannot only vary one parameter
What is a voltage clamp?
- 1 electrode monitors voltage on membrane with differential amplififier
- 1 electrode injects current proportional to injected change
What have voltage clamp experiments revealed about the K current?
- Slower to respond, must kick out positive current to counteract
What have voltage clamp experiments revealed about the Na current?
- Responds quickly to change and automatically turns itself off, even though it’s positive
What drugs can be used to block Na and K channels?
Na - TTX
K - TEA (less potent)
What effect do leakage channels cause in voltage-clamp experiments?
Small compared to other currents, must inject small ammount of positive current
What effect is seen on the Na current if current is increased slightly?
- Decreases more quickly but to the same level
- Due to more Na channels being opened but driving force remaining the same
Why is the K equilibrium potential harder to determine?
- As it is very negative and so at this negative voltage all channels are shut
- Take advantage of slow shutting, look at changes in current after you have opened them (“tail current”)
What effect does changing current level have on K channels?
See that membrane is more negative and so shut (but slowly)
What happens when you clamp a synapse at resting potential?
- Observe having to inject negative current
- Conclude increase in positive ions on the post-synaptic membrane
- Much faster, less capacitance
What are the problems with voltage clamp experiments?
- Voltage often differs along a neuron, want a good “space-clamp” where this isn’t an issue
What are the 6 principles of the Hodgkin-Huxley model of action potentials?
- Currents in action potentials due to electrochemical gradients (no pumps)
- Na and K flow through seperate channels
- Channels are either open or shut with no intermediates
- Each channel has 1 or more gates
- Channel is only open if all gates are open
- Each channel has 1st order kinetics with voltage dependent rate constants
i. e voltage gates open and close randomly, probability of being open is reliant on voltage
What did Hodgkin-Huxley propose as the two types of Na channel gate?
- Activation gate (m) opens quickly with depolarisation with 3 channels in series
- Inactivation gate (h) closes with slowly depolarisation, 1 gate
Sigmoid rise for activation, exponential drop for inactivation
What happens when the voltage dependent constants alpha and beta are large?
Rapid response to changes in voltage
What did Hodgkin-Huxley propose as the gate for K channels?
1 type of gate (n) which opens with depolarisation, 4 in series
Describe an action potential in terms of the ion channel gates opening and shutting
Resting - m likely to be shut, h likely to be open
Depolarising stimulus- opens m gate quickly, h gate slow to respond, Na ion inflow
Repolarisation - h gate closes and n (K) gate opens, outflow of K
Describe the absolute and relative refractory period in terms of ion channels opening and shutting
Absolute - second stimulus may open m gate but h gate stays shut as it is slow to respond
Relative - Na channel has returned to resting state by K channel is still open, excess conductance requires a stronger force to ellicit response
In what sense were Hodgkin-Huxley accurate?
Amino acids with charged side chains can act as voltage sensors enacting conformational changes on ion channels
In what sense were Hodgkin-Huxley innacurate?
Channels are not completely independent of eachother, probability of activation of one gate influences activation of other gates
Describe the Na channels and their gates
- alpha subunit is v-dependent formed from 4 repeating domains of of transmembrane alpha helixes
- Pore lining proteins have negative amino acids interact with Na+
- Sensors on S4 displace outwards with depolarisation opening the pore
- h gate residue can block channel for inactivation
Describe the K voltage dependent channel
- Structurally similar but no activation gate
How can channels be selectively permeable to Na or K?
Depend on hydration shells and not size
How can you patch clamp a channel?
- Electrode bonds to membrane with small patch with singular membrane
- Can manipulate where outside membrane is, therfore control of conditions
- Record current through singular ion channel
What has been shown from single patch-clamp recordings?
- Channels either open or shut
- Na and K currents made up of the summed conductance of Na and K channels opening and shutting
How does the chinese white shrimp have the fastest conduction?
- Fat fibre with thin axon and thick myelin sheath
- Conduct via penaid saltatory conduction, through fenestration node and submyelinic space
Where do Ca channels occur?
- Cell body (mediating intracellular signal)
- Synapses
What do Ca channels do?
Tells neuron how active it is (increases with depolarisation)
- Can function as pacemaker (sinoatrial node)
- Can regulate metabolism, muscle contraction and gene expression
Describe inactivating K channels
- Known as A-type
- Slow response to neuron in response to depolarisation
e. g in inking, takes prolonged stimulus to provoke
Describe Ca dependent K channels
- Can produce hyperpolarising pauses as well as make neurons fire bursts of spikes
- Does not need synaptic input
