Physiology of neurons Flashcards
Features of electrical synapses
- Faster
- Bidirectional
- Much smaller gap - 3.5nm
- No plasticity(few exceptions)
- No amplification
- Used for defensive reflexes(invertebrates), retina and brain
What is spatial summation
- 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
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(ie still slightly depolarised)
Describe the initial depolarisation part of an action potential
- Cell starts at rest(-70mV)
- Inward rectifier K+ channels are open, K+ flowing out is the dominant current
- Resting membrane potential is near Ek
- Few of the Na+ channels open and Na+ permeability increases
- Positive feedback loop with Na+ ions
- When the voltage goes above the threshold voltage(-50mV), the cell is committed to an AP
Describe the repolarisation stage of an action potential
- The positive feedback of an increase in sodium channel conductance and increase in voltage continues until the membrane becomes quite positive(>+30mV)
- When Vm>0, call this period the ‘overshoot’
- Na+ channel inactivation occurs
- Delayed rectifier k+ channels open –> increase in K+ going out
What is the refractory period
- Period of time during which neuron is inacapable of reinitiating an AP, the amount of time it takes for neuron’s membrane to be ready for a second stimlulus once it returns to its resting state following an excitation
- Refractory period occurs mostly during after-hyperpolarisation
What is AHP
- At the end of an AP, the voltage inside temporarily goes slightly more negative than at rest, follow by a return to the resting membrane potential
- When the voltage goes below -60mV, the inward rectifier K+ channels open again; they stay open until next depolarisation
- These normally clamp the voltage toward Ek, and are responsible for maintaining the resting membrane potential
- During AHP, there is an increase in K+ permeability and decrease in sodium permeability, the membrane potential moves closer to Ek
Why does the AHP occur?
- During the AHP, the voltage is more negative than at resting membrane potential
- During the AHP, the delayed rectifier K+ channels are still open, but at rest, they are closed
- The delayed rectifiers are open during the AHP because they are slow to close
- During the AHP, almost all of the Na+ channels are inactivated, at rest, there is a tiny amount of Na+ permeability
Effect of small lengthy(>10msec) synaptic currents on threshold potential
- They create a higher threshold potential generation than larger currents do
- This is due to accommodation of Na+ current(which inactivates during the slower subthreshold depolarization)
When are voltage gated channels open
- 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
Effect of lidocaine(lignocaine)
- Local anesthetic
- Raises the threshold and therefore lowers excitability which stops action potentials locally
- Lignocaine blocks sodium ion channels in pain neurons
- Lidocaine specifically blocks na+ channels in the inactivated state, not all sodium channels are blocked, only a percentage of them are blocked
Application of lidocaine
- Has to be be applied topically
Effect of carbamazepine(anticonvulsant)
- Carbamazepine inactivates sodium channels(has other actions as well)
- Raises AP threshold and lowers excitability throughout the brain(lowers excitability so lowers chance of an epileptic entering a seizure state)
Effect of antiarrhythmic drugs(class 1)
eg quinidine
- Works by lowering conduction velocity which extends the refractory period
- Na+ channel blocker
Effect of fugu fish(pufferfish) poison (tetrodotoxin TTX)
- Sodium channel blocker
- Inhibits action potential generation
What is carbamazepine used to treat
- is an anticonvulsant typically used for the treatment of seizure disorders and neuropathic pain
- Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to subsequently open, making brain cells less excitable; it also potentiates some GABA receptors
Effect of carbamazepine on cyp450
- Is a CYP450(3A4) inducer, and it may increase clearance of many drugs, decreasing their blood levels
- Drugs that are more rapidly metabolised with carbamazepine include carbamzepine(itself), warfarin, phenytoin, theophylline, valporic acid
What is the chemical force acting on an ion
- Also called diffusional force
- Is based upon the difference in concentration across the membrane
- eg if there is 10x as much Na+ outside than inside, the chemical force on Na+ channels is +60mV directed into the cell
What is the electrical force
- This is based on Vm(the membrane potential, which varies over time)
What is the equlibrium 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 is equal to the voltage(electrical) forces pushing K+ into the cell
what is used to calculate the equlibrium potential
- The nernst equation
Value of Ena
+60mV
Value of Ek
-90mV
Value of Eca
+123mV
Value of Ecl
-40mV(in neurons -65mV)
Features of action potentials
- A stereotyped electrical signal
- Short-duration
- In most neurons, skeletal and cardiomycotyes, a spike
- Always the same - ‘All or none’
- Require time to start because of conformational changes
- Action potentials = stereotyped electrical signal in excitable cells comprising a depolarisation and then a return to the resting voltage
Features of graded potentials
- Decrease as they move along
- Electrically localised
- Last a long time
- Much flatter in shape
- Are conducted almost instantly
- In receptor cells(eg rods and cones)
How is a signal re-amplified
• Electrotonic conduction(graded potentials) transmits signal along the length of the axon, the AP is a way for re-amplifying that signal
What is 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)
When is conduction velocity for neurons faster
• Faster when myelinated and larger diameter(lower resistance)
Speed and diameter of alpha motor fibres
100m/s for alpha motor fibres
myelinated 15 um diam
Speed and diameter of nociceptive fibres
1 m/s
unmyleinated 0.2-1.5um
Why does myelination make conduction velocity faster
- Because across the cell membrane capacitance is lower and resistance is higher
What is paresthesia
- refers to a burning or pricking sensation that is usually felt in the hands, arms, legs, or feet, but can also occur in other parts of the body
