lec 5 - neurophysiology

Question 1

Neurotransmission is regulated by channels located on distinct regions of the neuron:

Answer 1

Chemically-/Ligand-gated channels

Voltage-gated Na+ and K+ channels

Voltage-gated Ca2+ channels

Leakage Na+ and K+ channels

Question 2

Chemically-/Ligand-gated channels:

Answer 2

on dendrites and cell bodies to respond to neurotransmitter binding

also called ligand-gated ion channels

open or close in response to the binding of a ligand (i.e., a neurotransmitter) to a receptor.

Ligand-gated ion channels are preferentially distributed on the dendrites and cell body of the neuron

Question 3

Voltage-gated Na+ and K+ channels:

Answer 3

along axons to regulate action potential propagation

voltage (i.e., electrical) dependent, meaning they are opened at some membrane potentials and are closed at other membrane potentials.

These channels are generally ion selective

Question 4

Voltage-gated sodium and potassium channels =

Answer 4

major contributors to neuronal action potentials

highest concentration at the initial segment of the axon and at the nodes of Ranvier in myelinated axons

channels are absent in the dendrites and cell bodies

Question 5

Voltage-gated calcium channels =

Answer 5

important for neurotransmitter release

primarily found at axon/synaptic terminals as calcium is essential for releasing neurotransmitters into the synaptic cleft

Question 6

Leakage Na+ and K+ channels:

Answer 6

along entire neuron to contribute to resting membrane potential

Leakage channels are always open

ungated but are selective for ions

Leakage channels for potassium or sodium are present along the entire neuron membrane

Leakage channels use passive transport (do not require energy)

Question 7

____ channels establish the neuronal resting membrane potential

Answer 7

Potassium leakage

Question 8

Chemically-/Ligand-gated vs. voltage-gated channels

Answer 8

Chemically-/Ligand-gated channels
> Closed under normal conditions (resting membrane potential)
> Selective binding of neurotransmitters opens channel

Voltage-gated channels
> Closed under normal conditions
> Change in membrane voltage opens channel

Question 9

Chemically-/Ligand-gated channels
Distinct ion selectivity and open time:

Answer 9

ACh and NMDA receptors: Na+ influx
> excitatory NT’s cause depolarization

GABA receptors: Cl- influx and K+ efflux
> inhibitory NT’s cause hyperpolarization

Question 10

Voltage-gated channels
Distinct ion selectivity and open time:

Answer 10

Voltage-gated Na+ channel: Na+ influx

Voltage-gated K+ channel: K+ efflux

Voltage-gated Ca2+ channel: Ca2+ influx

Question 11

Na+/K+ pump (Na+/K+ ATPase)

Answer 11

Pumps 3 Na+ out of neuron and 2 K+ into neuron

Uses ATP to pump Na+ and K+ against their electrochemical gradients

Restores resting membrane potential after an action potential

Question 12

Ca2+ pump (Ca2+ ATPase)

Answer 12

Pumps Ca2+ out of neuron

Uses ATP to pump Ca2+ against its electrochemical gradient

Restores Ca2+ concentration after Ca2+ influx for neurotransmitter release

Question 13

In addition to ligand-gated, voltage-gated, and leakage channels, the neuronal membrane also contains pumps that move ions against their chemical gradient and, thus, require energy (e.g., ATP)

Answer 13

sodium enters the neuron and potassium exits the neuron during an action potential

ions must get back to where they started = movement is moving against their concentration gradient

must be pumped back using an energy dependent process

sodium and potassium will be pumped using the sodium-potassium ATPase/pump, which uses ATP to pump three sodium ions out of the cell and two potassium ions into the cell

In addition to restoring the sodium and potassium concentrations (via the sodium-potassium pump), calcium concentration must be restored after the calcium influx at the synaptic/axon terminal to promote neurotransmitter release

calcium-ATPase/pump pumps calcium ions out of the neuron to restore the intracellular calcium concentration

Question 14

Membrane potential (V):

Answer 14

voltage inside cell relative to outside cell

Question 15

Resting membrane potential (RMP):

Answer 15

membrane potential of a resting cell

Question 16

Depolarization:

Answer 16

membrane potential becomes more positive

Question 17

Hyperpolarization:

Answer 17

membrane potential becomes more negative

Question 18

Membrane resistance (R):

Answer 18

resistance the membrane has to ion flow

Question 19

Current (I):

Answer 19

flow of electrical charge

Neurons carry electrical current in the form of ions travelling across the membrane

Question 20

Neurons carry electrical current in the form of ions with positive ___ or negative___ charges

Answer 20

(cations)
(anions)

Question 21

Ions are located in ____ as well as the ____. The ions are separated by a ____. This separation of charge creates a ____ across the membrane. The difference in charge is referred to as the ____.

Answer 21

neuronal cytoplasm
interstitial fluid
plasma membrane
”potential” difference
membrane potential (V)

Question 22

Even in the absence of any synaptic input there is a potential difference between the inside and outside of the neuron. The membrane potential in an inactive/resting neuron without any synaptic stimulation is called the ____

Answer 22

resting membrane potential

Question 23

When synaptic input occurs, the inside of the neuron can become more positive ___ or more negative ___ relative to the resting state.

Answer 23

(depolarized)
(hyperpolarized)

Question 24

The membrane also acts as a capacitor to separate charge and resist the flow of ions across the membrane. The ___ is defined as the amount of resistance to ion flow. The number, type, and permeability of channels and pumps on the plasma membrane changes the membrane resistance. ___ increases membrane resistance, as it further separates the charge of the cytoplasm Internal neuronal environment) and the charge of the interstitial fluid (external environment). Thus, myelin makes it ___ for ions to flow through the plasma membrane.

Answer 24

membrane resistance
Myelin
harder

Question 25

Neuronal RMP

Answer 25

Most neurons have a resting membrane potential (RMP) of -70mV

More K+ and protein anions inside the neuron than outside

More Na+, Ca2+, and Cl- outside the neuron than inside

K+ leakage channels are located throughout the neuronal membrane and are always open, allowing K+ to flow down its chemical gradient and leave the neuron

Question 26

Neurons have a differential distribution of ions across the plasma membrane:

Answer 26

approximately 30 times more potassium inside a neuron than outside a neuron

about 10 times more sodium outside a neuron than inside a neuron

more chloride and calcium ions outside the neuron than inside the neuron

Question 27

There are more ___ proteins inside the neuron compared to outside the neuron and these proteins are ___ to the membrane.

Answer 27

negative
impermeable

Question 28

Neuronal RMP Mechanisms

Answer 28

K+ leakage channels establish the RMP by allowing K+ diffusion down its chemical gradient (efflux)
> Neuronal membranes have fewer Na+ leakage channels
> RMP is closer to EK than ENa

Na +/K+ ATPase maintains and restores the RMP by pumping 2 K+ in and 3 Na+ out against their electrochemical gradient

Question 29

Changes in RMP can produce 2 types of signals:

Answer 29

graded potentials and action potentials

Question 30

Graded Potentials

Answer 30

passive currents

The degree of the potential is based on the magnitude of the stimulus

The intensity of the signal decays with distance

Graded potentials include EPSPs and IPSPs

Question 31

Synaptic inputs on the dendrite or cell body release neurotransmitters (NTs) that bind to ligand-gated channels on the post-synaptic membrane:

Answer 31

> channel pore opens
ions enter or leave the neuron
creates a local excitatory post-synaptic potential (EPSP) = causes depolarization
or
creates a local inhibitory post-synaptic potential (IPSP) = causes hyperpolarization

The degree of the potential is based on the magnitude of the stimulus (e.g., dropping a small pebble in a pond vs. dropping a large rock in a pond)

Question 32

we refer to the potential created by synaptic inputs as graded potentials because

Answer 32

they can be of different sizes and can be summed to reach a critical threshold value

Question 33

The locally injected current spreads through the neuron’s cytoplasm (much like the waves created by dropping a pebble or rock into a pond). The current decays with distance from the site of current injection (i.e., synapse location). This decay is due to two currents:

Answer 33

Ohmic current: ions exiting through leakage channels at the site of stimulation

Capacitive current: ions moving through the cytoplasm before exiting at other leakage channels

This differs from action potentials, in which current spreads over long distances using an all-or-none mechanism

Question 34

Excitatory Post-Synaptic Potential (EPSP)

Answer 34

Excitatory NT binds to its receptor and opens a ligand-gated channel

Na+ moves into the cell, causing depolarization

EPSPs bring neuronal membrane potential closer to threshold

EPSPs mostly occur on dendritic spines

Question 35

Inhibitory Post-Synaptic Potential (IPSP)

Answer 35

Inhibitory NT binds to its receptor and opens a ligand-gated channel
> K+ channel allowing K+ efflux
> Cl- channel allowing Cl- influx

K+ efflux or Cl- influx causes hyperpolarization

IPSPs take neuronal membrane potential further away from threshold

IPSPs mostly occur on dendritic shafts and neuronal cell bodies

Question 36

Threshold Potential

Answer 36

Action potentials are regulated by spatiotemporal changes in membrane potential

Reaching the threshold potential for opening of voltage-gated Na+ channels is key for action potential generation

Question 37

Summation of Graded Potentials

Answer 37

Graded potentials must be summed to reach threshold

Neurons have thousands of synapses on their dendrites and cell bodies

Some of these synapses are excitatory and some are inhibitory

The sum of all these synapses determines if an action potential will fire or not

Question 38

Action Potentials

Answer 38

mediated by voltage-gated Na+ channels and voltage-gated K+ channels

In contrast to graded potentials, which are mediated by leakage channels (mostly potassium leakage channels), action potentials are mediated by voltage-gated channels, including both sodium voltage-gated channels and potassium voltage-gated channels

Once all the graded potentials created by synaptic input and local depolarization reach threshold, the neuron will depolarize due to influx of sodium ions through voltage-gated sodium channels

Once voltage-gated sodium channels are inactivated (inactivation gate blocks channel pore), no more sodium can enter the neuron

Question 39

Voltage-gated potassium channels open to allow potassium efflux, resulting in ___ to the resting membrane potential. However, potassium channels stay open longer, resulting in more potassium entering than necessary, causing ___ below the resting membrane potential.

Answer 39

repolarization
hyperpolarization

Question 40

Action potentials are all-or-none

Answer 40

Once threshold is reached, an action potential is initiated

If threshold is not reached, no action potential is initiated

Action potentials do not get bigger with greater depolarization

Unlike graded potentials, where the current can be summed, once threshold is reached for an action potential, the response is all or none

making the stimulus greater or larger does not cause a larger (greater amplitude) action potential.

Question 41

Voltage-Gated Na+ Channel

Answer 41

Selective for Na+

Two gates: activation and inactivation gate

Three states: closed, opened, and inactivated

closed at resting state - no Na+ enters the cell through them

opened by depolariazation - Na+ can center the cell

inactivated - channels automatically blocked by inactivation gates soon after they open

Question 42

Voltage-gated sodium channels have gating mechanisms that block the channel pore

the two gates creates three potential states for this channel:

Answer 42

Open and allowing sodium influx = activation gate and inactivation gate are open

Inactive = inactivation gate blocking the pore
> no matter how strong the stimulus is, the pore cannot be opened
> occurs during the absolute refractory period
> No action potential can be initiated during this time

Closed but ready to be opened to allow sodium influx = inactivation gate is open, but the activation gate is closed
> occurs during the relative refractory period
> action potential can occur here, but it requires a larger stimulus

Question 43

Voltage-Gated K+ Channel

Answer 43

Selective for K+

One gate: voltage sensitive gate

Two states: closed and opened

Opening is delayed compared to opening of voltage-gated Na+ channel

Question 44

Voltage-gated potassium channels lack an inactivation gate; thus, they have a single gate and two possible states

Answer 44

Closed: no ion flow, but ready to be opened
> Gate is closed
> closed at resting state so no K+ exits the cell

Open: allow potassium efflux
> Gate is open
> opening for voltage-gated potassium channels is delayed relative to the opening of the voltage-gated sodium channels
> opened by depolarization, after a delay, K+ exits the cell

Question 45

Action Potentials
5 Steps

Answer 45

1) a local potential depolarizes the axolemma of the axon hillock to threshold

2) voltage-gated Na+ channels activate, Na+ enter, axon section depolarizes

3) Na+ channels inactivate and voltage-gated K+ channels activate = Na+ stops entering and K+ exits the axon = repolarization begins

4) Na+ channels return to the resting state = repolarization continues

5) axolemma may hyperpolarize before K+ channels return to resting state = after, axolemma returns to resting membrane potential

Question 46

Absolute refractory period:

Answer 46

no action potential can be initiated

Voltage-gated Na+ channels are inactivated

Lasts about 1-2msec

Keeps unidirectional flow of action potentials

Question 47

Relative refractory period:

Answer 47

an action potential can be generated, but it requires a stronger stimulus

Voltage-gated Na+ channels are closed

Lasts about 4msec

Question 48

Action Potential Frequency

Answer 48

determined by stimulus intensity

Stronger stimulus = increases neuro-transmitter release = increases action potential frequency

limited by absolute refractory period

Question 49

Conduction velocity is dependent on two factors:

Answer 49

Axon diameter: larger diameter = decreased resistance to current flow = faster signal velocity

Axon myelination: myelin increases membrane resistance, which increase signal velocity

Question 50

Axon myelination:

Answer 50

More important factor impacting conduction velocity

This leakage property leads to the decay of the action potential over a distance

myelin covers the leakage channels, therefore, current flows down the axon rather than out of the neuron

Question 51

Saltatory conduction:

Answer 51

action potential only regenerates at nodes of Ranvier, where voltage-gated Na+ channels are exposed, resulting in faster velocity

Question 52

neurons have leakage channels throughout their entirety, and that there are more ___ leakage channels than ___ leakage channels; thus, more potassium ___ than sodium ___. Thus, the cell becomes more negative (___) and may not have enough current to activate the next voltage-gated sodium channels further down the axon.

Answer 52

potassium
sodium
leaks out
leaks in
hyperpolarized

Question 53

Demyelinating diseases affecting the CNS

Answer 53

Multiple sclerosis (MS): chronic progressive inflammatory disease, causing CNS demyelination

Question 54

Demyelinating diseases affecting the PNS

Answer 54

Guillain-Barré syndrome: acute immune-mediated disease caused by infections (e.g., Epstein-Barr or influenza virus) that results in PNS demyelination

Charcot Marie Tooth (CMT): genetic disease that causes peripheral demyelination