IC2 Signaling, Action Potential, Synaptic Transmission

Question 1

Explain conduction

Answer 1

Neurons send electrical signals (action potential) along axons

*Conduct impulses

Question 2

Action potential occurs when __________ channels ______, altering membrane permeability of ____ and ____

Answer 2

Voltage gated ion channels open, altering membrane permeability of Na+ and K+

Question 3

Action potential

• What is resting membrane potential

Answer 3

RMP -60mV

• More negative inside the membrane compared to outside the membrane (reflects the unequal distribution of charges)
• Intracellular K+ > Extraccellular K+,
• Intracellular Na+, Cl-, Ca2+ < Extracellular Na+, Cl-, Ca2+

At RMP, there is continuous diffusion of ions, net movement of all ions in and out is at equilibrium

Question 4

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 1

Answer 4

Resting membrane potential

• Na+/K+ pump maintains the RMP via differential distribution of K+, Na+, Cl- ions across the membrane

Question 5

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 2

Answer 5

Depolarization

• Action potential begins when a graded/depolarizing potential reaches the trigger zone and depolarizes the membrane
• Membrane depolarization is typically evoked due to Excitatory postsynaptic potential (EPSP) at synapse
• Opening of ligand-gated channels by excitatory neurotransmitter released at the neuromuscular junction (NMJ) and at synapses within the CNS (referring to postsynaptic membrane)

Question 6

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 3

Answer 6

Threshold membrane potential

• Cell depolarizes to threshold membrane potential (-40mV), voltage gated Na+ channels are activated/opened
• Initiation of action potential occurs at Phase 3

Question 7

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 4

Answer 7

Rising phase

• Rapid Na+ entry into the cell depolarizes the cell

Question 8

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 5

Answer 8

Overshoot phase

• Inside of the cell becomes more positive than the outside, thereby reversing the membrane potential polarity

Question 9

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 6

Answer 9

Falling phase

• Voltage gated Na+ channels are inactivated
• Positive membrane potential causes voltage gated K+ channels to open
• K+ moves out of the cell
• Membrane potential repolarizes
• Refractory period (inactivation of Na+ conduction and opening of K+ conductance causes a period of time during which cell is incapable of repeating an action potential)

Question 10

7 phases of Action Potential
(describe polarization, opening/closing of channels etc.)

• Phase 7

Answer 10

Recovery phase

• Occurs as voltage gated K+ channels close
• Repolarize back to RMP
• Transient hyperpolarization (after potential) may occur as it takes a few msec for K conductance to decrease after membrane has returned to resting levels

Question 11

What are the two forces that contribute to equilibrium potential?

Answer 11

1. Concentration gradient (favors efflux of K+)
2. Electrical gradient (favour influx of K+)

=> Electrochemical gradient acting on the ion determines the equilibrium potential of the ion

Question 12

What is equilibrium potential?

Are ions at EP at RMP?

Answer 12

Potential at which the outward and inward gradients acting on the ion balance out, and there is no net movement of the ion across the membrane

No, ions are NOT at equilibrium potential at RMP as there is still continuous diffusion and net movement of the ions. A given ion will either move in or out of the cell with the intention of pushing the membrane potential towards its E value.

(E.g., Potassium E = -97mV, at RMP, K+ ions will move out of the cell to push -65mV to -97mV)

Question 13

How to calculate equilibrium potential?

Answer 13

E = 58 log (conc. outside / conc. inside)

If E is more negative than RMP => efflux of K+

If E is more positive than RMP => influx of K+

Question 14

The eventual RMP of -65mV reflects the greater permeability of ______

Answer 14

The negative RMP reflects the greater permeability of Potassium out of cell (due to a class of permanently opened ‘leak’ potassium channels in the membrane)

Question 15

How does Hyperkalemia (50mM) affect EP and RMP?

Consequences?

Answer 15

Concentration gradient becomes less steep as the extracellular concentration of K+ increases (still efflux but much less)

EP becomes less negative, less efflux

=> greater accumulation of positive charge intracellularly

RMP eventually becomes less negative (depolarizes to a new value), cell becomes HYPEREXCITABLE

Question 16

How does Hypokalemia affect EP and RMP?

Consequences?

Answer 16

Less potassium outside cell, concentration gradient becomes more steep, favours efflux

E becomes more negative (efflux)
=> Less K+ in cell

RMP becomes more negative, hyperpolarization of the RMP, cell is less excitable

• Muscle weakness and paralysis of skeletal muscles, due to decreased ability of muscle to contract
• Other symptoms: lassitude, impairment of respiratory function
• Thus, important to look out for hypokalemia due to thiazide/loop diuretics, metabolic alkalosis, diarrhea

Question 17

What is the neuromuscular junction?

Answer 17

Chemical synaptic connection between terminal end (axon) of a motor neuron and a skeletal/smooth/cardiac muscle fiber

Narrow muscular junction is a chemical synapse where the axon terminals of motor neurons meet the motor end plate of a skeletal muscle fiber

Site of transmission of action potential from NERVE TO MUSCLE => causing muscle to contract

Question 18

Compare and contrast the two types of synapses

Answer 18

1. Electrical

• Synaptic cleft is small 0.2nm
• Current (ions) generated in the presynaptic neuron flows directly into the postsynaptic cell through gap-junction channels or low resistance bridges
• Transmission is 2 way
• Transmission is faster

2. Chemical

• No structural continuity between pre and postsynaptic elements
• Separated by synaptic cleft of 20-40nm
• Action potential in presynaptic cell must release chemical neurotransmitters in the cleft
• Transmitter diffuses across the cleft to interact with specific receptors that either depolarize/hyperpolarize the postsynaptic cell
• Transmission is 1 way
• Transmission is slower

Question 19

Process of chemical synaptic transmission

Explain the first step in presynaptic membrane

Answer 19

1. Receptive step

• Activated by arrival of action potential at presynaptic axon terminal
• Action potential depolarizes the presynaptic membrane, leading to opening of voltage gated Ca2+ channels
• Influx of Ca2+ into presynaptic terminal, act on Ca2+ sensitive vesicle associated membrane proteins to release vesicles from cytoskeleton, and facilitates fusion of synaptic vesicle with the presynaptic membrane
• Release (exocytosis) of transmitter acetylcholine into the synaptic cleft

Question 20

Process of chemical synaptic transmission

Explain the second step in postsynaptic membrane

Answer 20

2. Transmitting step

-Starts with the binding of acetylcholine to postsynaptic ligand-gated receptor/ion channels (GPCRs / ion channels) on the postsynaptic membrane of dendrites
- Postsynaptic membrane depolarizes leading to generation of action potential through voltage-gated sodium channels (7 phases)

Question 21

How do signals get terminated?

Answer 21

• Enzymatic break down/catabolism
• Reuptake by presynaptic neuron (negative feedback)
• Astrocytic process - metabolism of neurotransmitters (glutamate)

Question 22

What are the postsynaptic targets for excitatory vs inhibitory synapse?

Answer 22

Excitatory: dendrite

• e.g., release of glutamate (CNS), acetylcholine (NMJ)

Inhibitory: soma (cell body)

• e.g., release of GABA

Question 23

What is the action of GABA?

Answer 23

GABA activates Cl- channels, causing influx of Cl- into the cell, therefore causing hyperpolarization of the cell which makes it less excitable

Question 24

What is excitatory postsynaptic potential (EPSP)?

Answer 24

Depolarization of postsynaptic membrane due to release of excitatory transmitter from presynaptic axon terminal to the dendrite of the neuron

Represented by phase 2 of action potential (depolarization phase)

Question 25

What is inhibitory postsynaptic potential (IPSP)?

Answer 25

Hyperpolarization of the postsynaptic membrane induced by inhibitory transmitters such as GABA

Question 26

How might epileptic focus and seizures occur?

Answer 26

Epileptic focus may occur when IPSP is compromised, leading to unchecked excitation

Abnormal activity in small areas of cortex (foci) can spread to other synaptically connected region, triggering a seizure

Hyperexcitability such as the rhythmic firing of a relatively large population of neurons can lead to seizure

Question 27

CONCLUSION:

Two ways in which action potential is generated

Answer 27

1. External stimulus applied (SIGNAL TRANSDUCTION - AFFERENT NERVE FIBERS)

• Sensory transduction: external stimulus => electrical charge/signal
• Electrical charge causes net influx of ions, depolarization, leading to AP generation when threshold membrane potential is reached at the trigger point
• AP relayed to CNS, leading to sensation

2. Information is transferred to neuron (SYNAPTIC TRANSMISSION - NEURONS)

• Synaptic transmission (EPSP or IPSP)
• EPSP lead to release of excitatory neurotransmitters which open ligand-gated receptor/ion channels, leading to depolarization => open voltage gated Na+ channels => generate AP

Question 28

How might disease result form interruption of signal?

Answer 28

• Disruption of action potential signal
• Lesion of the region = trauma
• Degeneration of cells, alteration of neurochemistry = ageing/disease