Physiology of neurons

Question 1

Features of electrical synapses

Answer 1

• Faster
• Bidirectional
• Much smaller gap - 3.5nm
• No plasticity(few exceptions)
• No amplification
• Used for defensive reflexes(invertebrates), retina and brain

Question 2

What is spatial summation

Answer 2

• 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

Question 3

What is temporal summation

Answer 3

• 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)

Question 4

Describe the initial depolarisation part of an action potential

Answer 4

• 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

Question 5

Describe the repolarisation stage of an action potential

Answer 5

• 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

Question 6

What is the refractory period

Answer 6

• 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

Question 7

What is AHP

Answer 7

• 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

Question 8

Why does the AHP occur?

Answer 8

• 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

Question 9

Effect of small lengthy(>10msec) synaptic currents on threshold potential

Answer 9

• 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)

Question 10

When are voltage gated channels open

Answer 10

• 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

Question 11

Effect of lidocaine(lignocaine)

Answer 11

• 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

Question 12

Application of lidocaine

Answer 12

• Has to be be applied topically

Question 13

Effect of carbamazepine(anticonvulsant)

Answer 13

• 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)

Question 14

Effect of antiarrhythmic drugs(class 1)

Answer 14

eg quinidine

• Works by lowering conduction velocity which extends the refractory period
• Na+ channel blocker

Question 15

Effect of fugu fish(pufferfish) poison (tetrodotoxin TTX)

Answer 15

• Sodium channel blocker

- Inhibits action potential generation

Question 16

What is carbamazepine used to treat

Answer 16

• 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

Question 17

Effect of carbamazepine on cyp450

Answer 17

• 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

Question 18

What is the chemical force acting on an ion

Answer 18

• 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

Question 19

What is the electrical force

Answer 19

• This is based on Vm(the membrane potential, which varies over time)

Question 20

What is the equlibrium potential

Answer 20

• 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

Question 21

what is used to calculate the equlibrium potential

Answer 21

• The nernst equation

Question 22

Value of Ena

Answer 22

+60mV

Question 23

Value of Ek

Answer 23

-90mV

Question 24

Value of Eca

Answer 24

+123mV

Question 25

Value of Ecl

Answer 25

-40mV(in neurons -65mV)

Question 26

Features of action potentials

Answer 26

• 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

Question 27

Features of graded potentials

Answer 27

• 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)

Question 28

How is a signal re-amplified

Answer 28

• Electrotonic conduction(graded potentials) transmits signal along the length of the axon, the AP is a way for re-amplifying that signal

Question 29

What is saltatory conduction

Answer 29

• 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)

Question 30

When is conduction velocity for neurons faster

Answer 30

• Faster when myelinated and larger diameter(lower resistance)

Question 31

Speed and diameter of alpha motor fibres

Answer 31

100m/s for alpha motor fibres

myelinated 15 um diam

Question 32

Speed and diameter of nociceptive fibres

Answer 32

1 m/s

unmyleinated 0.2-1.5um

Question 33

Why does myelination make conduction velocity faster

Answer 33

• Because across the cell membrane capacitance is lower and resistance is higher

Question 34

What is paresthesia

Answer 34

• 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