T1 L5:Physiology of Neurons Flashcards
give some features of electrical synapses
1- faster
2-bidirectional
3-much smaller gap=3.5nm
4- no plasticity
5- no amplification
why can’t an electrical synapse be amplified?
1- Signal is always weakened as it is transmitted from pre-synaptic to post-synaptic cell
what 2 thing can’t happen with the signal of an electrical synapse
1- Signal will not transmit if post-synaptic cell is much bigger than pre-synaptic cells
2- Excitatory pre-synaptic signal cannot inhibit the post-synaptic cell
what is spatial summation
1- A neuron determines whether to fire based on the “add together” of all the tiny signals it is receiving from several other neurons synapsing on it (from both excitatory and inhibitory inputs). In this way small depolarisations (if there are many) can reach threshold
See diagram of convergent neuronal signalling
what is temporal summation
When the input neuron is firing fast enough so that the receiving neuron can “add together” the many tiny signals, ultimately reaching threshold.
This happens when the receiving neuron’s ability to recover from the tiny input (depolarisation) is slow enough that the next signal arrives while the receiving neuron has not yet recovered from the previous signal (i.e. it is still slightly depolarized)
look at AP outline in slide 7
- how was it
describe an AP (4 marks)
At rest K+ that is going out of cell clamps the membrane potential negative (e.g. -70 mV)
An external factor (e.g. synaptic activity) causes the membrane to depolarise slightly. If the voltage reaches threshold, then
Na+ conductance shoots up, Na+ current goes into cell, membrane potential depolarises (voltage +)
With a time-delay, Na+ conduction diminishes (inactivation), K+ conductance increases, so K+ leaves cell, voltage returns to resting potential (i.e. the membrane repolarises)
describe how initially the neuron is depolarised
The cell starts at rest (-70 mV)
Inward rectifier K+ channels are open, K+ flowing out is the dominant current
Resting membrane potential is near EK
Something causes the cell to become less negative:
Depolarisation: inside the cell the voltage becomes less negative (or more positive)
Could be a nearby cell depolarising
Could be synaptic transmission where a neurotransmitter opens a ligand-gated channel
what is the positive feedback loop of a depolarisation
-The initial depolarisation causes a few of the Na+ channels to open
Na+ permeability increases, Na+ current flows through channels into cell
The additional current of Na+ going into the cell more depolarisation (ie the membrane potential moves closer to 0 mV)
This acts as a positive feedback loop
When the voltage goes above the threshold voltage (-50 mV), the cell is committed to an AP
APs are “all-or-none”.
The positive feedback of ↑ Na+ channel conductance and ↑ voltage continues until the membrane becomes quite positive (> +30 mV)
when Vm > 0, call this period the “overshoot”
describe a refractory period
period of time during which neuron is incapable of reinitiating an AP,
the amount of time it takes for neuron’s membrane to be ready for a second stimulus once it returns to its resting state following an excitation
Refractory period occurs mostly during after-hyperpolarisation
if APs are al or none (they carry no information about the size of the stimulus that elicited them
) how do they code for the intensity of their synaptic input
1- Firing frequency represents the intensity of activity:
- Increasing threshold lowers firing frequency (see figure)
- Increasing excitatory synaptic activity increases firing frequency
- When lengthy (>10 msec) synaptic currents are small, they create a higher threshold potential for action potential generation than larger currents do,
- This is due to accommodation of Na+ current (which inactivates during the slower subthreshold depolarization)
2-Different neurons for different strength stimuli:
-Light touch receptors vs. pain receptors (see sensory receptor lectures)
what occurs with increased threshold
- a decrease in excitability
what is threshold
- voltage above which action potential fires
what is the basis for psychotropic pharmacology
- excitability changes
describe why voltage-gated channels change states based on TM voltage
- These channels open when membrane becomes positive inside
- Channels in the open state can conduct = increased permeability
- Inward rectifiers are the opposite of other channels
- Channels close when membrane repolarises
what’s the difference between an inactivated channel and a closed channel
Inactivated channel = when membrane is positive, channel tends to stop conducting.
Closed channel = when membrane is negative, channel tends to stop conducting.
what does the voltage depend on
-
at rest, Vm=
~Ek
describe lidocaine
- local anaesthetic
- apply topically
- Raises the threshold
,And thus lowers excitability
,Which stops action potentials locally
-Lidocaine specifically blocks Na+ channels in the inactivated state
describe carbamazepine
- anticonvulsant
- Carbamazepine inactivates sodium channels
- Raises AP threshold and Lowers excitability
-
describe an antiarrhythmic drug
- quinidine
- works by lowering conduction velocity
- which extends the refractory period
what’s the difference between the 2 forces on each ion
1- chemical force:
Also called diffusional force
Is based upon the difference in concentration across the membrane
E.g. If there is 10X as much Na+ outside than inside, the chemical force on Na+ channels is 60 mV directed into the cell
2- The electrical force
This is based on Vm (the membrane potential, which varies over time)
look at slide 24
-how was it
what is the Ek-
The Equilibrium Potential
describe the Equilibrium Potential
EK is also called the reversal potential of K+.
- EK is the voltage where K+ flowing out = K+ flowing in because electrochemical forces on K+ are in equilibrium
- This occurs when the diffusion (chemical) forces pushing K+ out of the cell equal the voltage (electrical) forces pushing K+ into the cell
give some common equilibrium potentials
ENa = +60 mV
EK = -90 mV
ECa = +123 mV
ECl = -40 mV (in neurons –65 mV)
give a mnemonic for equilibrium potentials
A CAt is as easy as 1-2-3
A NAg retires early at 60.
A CLub for fighting Ali Baba’s 40 thieves
A King will die at 90.
what is the difference between graded action potentials and action potentials
AP:
- A Stereotyped electrical signal
- Short-duration
- in most neurons, skeletal and cardiomyocytes
- Always the same — “All or none”
- Require time to start because of conformational changes
Electrically localised
Last a long time
much Flatter in shape
Are conducted almost instantly
in receptor cells (eg rods & cones)
variable -in duration and voltage
describe a graded potential
- Changes in membrane potential do not propagate very far via passive electrical forces
Voltage signals diminish as you go farther from the source
This happens because the axon has a finite resistance
For mV changes of cells and APs, the change would be all but extinguished in 1 cm
Electrotonic conduction (graded potentials) transmits signal along the length of the axon. The AP is a way for re-amplifying that signal
describe saltatory conduction
- When the action potential “jumps” from Node to Node
- Net effect = faster conduction velocity
- The electrotonic jumps between nodes are very fast.
-Initiating an Action Potential at each node is slower
Conformational change of ion channels
what factors affect conduction velocity and how
faster when:
- axon is myelinated
- larger diameter of axon
what are the typical conduction velocities for alpha and c neurons
- Alpha motor fibres: 100 m/s for myelinated, 15 um diam
- for C nociceptive fibres :1 m/s for unmyelinated, 0.2 - 1.5 um