Transport: How Electrifying Flashcards
Lecture 18 (101 cards)
1
Q
What are the 3 ways the free energy of gradients can be utilized?
A
- Co-transport - Up gradient transport of other molecules (symporters, antiporters)
- Production of electrical signals
- Chemiosmotic coupling
2
Q
What are the 3 ways potential energy is stored?
A
- High energy bonds - ATP, GTP (phosphoanhydride bonds cleaved, release energy)
- Concentration gradients (high to low concentration of ions can drive the movement of other molecules)
- Charge gradients (electric potential
3
Q
Which is easier, for Na+ to leak inside the cell or for K+ to leak outside the cell?
A
There is an open leak channel for K+ ions to exit the cell.
4
Q
How many K+ ions are pumped into the cell per ATP by the sodium-potassium pump?
A
2 K+
5
Q
How many Na+ ions are pumped out of the cell per ATP by the sodium-potassium pump?
A
3 Na+
6
Q
Why is the plasma membrane permeable to potassium, but not sodium?
A
There is a potassium leak channel in the PM that is always open and moves K+ down its concentration and electrochemical gradient.
7
Q
What is membrane potential? What establishes it?
A
Membrane potential is an electric gradient or gradient of charge.
MP is established by the conductance of charge via ion transport across a membrane (separation of negative charges on one side and positive charges on other side of a membrane).
8
Q
Is the concentration gradient and the membrane potential of potassium across the plasma membrane allied or opposing?
A
Opposing. K+ is flowing down the concentration gradient via the potassium leak channel, but the membrane potential moves in the opposite direction because only the positive K+ charges are moving past the membrane. The positive charges want to rejoin the remaining negatively charged macromolecules, in opposition to their concentration gradient.
9
Q
Why do only positive ions leak across the membrane?
A
Because K+ ions are smaller than the large macromolecules with negative charges (proteins and nucleic acids).
10
Q
Membranes act as capacitors. What are capacitors?
A
11
Q
How thick are biological membranes? What electrochemical implication does this have?
A
4-6 nm. Membrane thinness means negative and positive charges can sense excess charges on other side of membranes, causing them to line up.
12
Q
What is the resting (equilibrium) membrane potential? Why?
A
-60 to -200 mV. Cells at rest usually have an excess of negative ions with an excess of positive ions outside the plasma membrane.
13
Q
Why is the resting membrane potential negative (-60 to -200 mV)?
A
Due to K+ leaking (diffusing) out of the cell, leaving negative charges inside the cell. This resting potential is maintained by resting K+ channels.
14
Q
What is the charge of the bulk solution of cytoplasm around the cell?
A
Neutral, no charge due to an even mix between positive and negative charges
15
Q
How to measure the separation of charge across a membrane?
A
Put an electrode inside the cell and another outside of the cell. Measure the voltage difference across the membrane with a potentiometer.
16
Q
Which two factors influence the membrane potential?
A
- electrochemical gradient
- rate at which ions are conducted across the membrane
17
Q
Where is the calcium concentration greatest, inside or outside the cell?
A
3-4 orders of magnitude greater outside of the cell
18
Q
Where is the sodium concentration greatest, inside or outside the cell?
A
An order of magnitude greater outside the cell
19
Q
Where is the potassium concentration greatest, inside or outside the cell?
A
inside the cell
20
Q
Where is the synapse?
A
the gap between the pre-synaptic and post-synaptic cell
21
Q
What kind of signal moves through a synpase?
A
chemical signal
22
Q
What kind of signals are processed by the neurons?
A
electrical signals
23
Q
Describe the process of cell signaling between neurons.
A
- Depolarization event in first neuron. An influx of positive charges in the cell causes the internal voltage of the first neuron to become positive.
- Step 1 activates a voltage-gated calcium channel, causing calcium to enter the cell.
- Calcium influx triggers regulated exocytosis; The calcium binds to proteins associated with the 20 neurosecretory vesicles that are already filled with neurotransmitters and docked at the plasma membrane via SNARE proteins. After binding, the vesicles move to the end of the neuron and release the acetylcholine neurotransmitters.
- Acetylcholine binds to a ligand-gated sodium channel protein on the postsynaptic neuron, causing it to open.
- After Step 4, sodium rushes into the cell, but does not cause a massive depolarization in the cell. The resting membrane potential begins to increase, having a big local effect (but a small broader effect).
- After the small influx of Na+ ions, local depolarization causes voltage-gated sodium channels to open, resulting in a massive influx of Na_ ions and a change in membrane potential from -60 mV to +40 mV.
- Repolarization
- Hyperpolarization
- Return to normalcy
24
Q
What is a depolarization event?
A
when the membrane potential of a neuron becomes less negative
25
Which voltage-gated channels are open during the resting state?
Neither.
26
Describe the state of the voltage-gated channels during depolarization.
Na+ channels are open and K+ channels are closed.
27
Describe the state of the voltage-gated channels during repolarization.
Na+ channels are inactivated and K+ channels are open.
28
Describe the state of the voltage-gated channels during hyperpolarization.
Na+ channels are closed and K+ channels are open; ends when the K+ channel closes and ions move passively
29
What is a hyperpolarization event?
when the membrane potential of a neuron becomes more negative
30
What causes the voltage-gated Na+ channel to open?
initial localized change in membrane potential across the post-synaptic membrane
31
What causes the ligand-gated channel to open?
when a particular molecule binds to the channel
32
What causes the initial localized change across the post-synaptic membrane that ultimately causes the voltage-gated Na+ channel to open?
The acetylcholine neurotransmitter is released from the secretory vesicles and binds to the receptor protein (ligand-gated channel), causing it to open, allowing a small influx of Na+ ions.
33
Describe how voltage-gated Na+ channels work.
1. Initial depolarization due to influx of Na+ ions causes a conformational change in voltage-sensing alpha helices, resulting in the opening of the channel in the span of less than 0.1 ms.
2. After the channel opens, the voltage-sensing alpha helices return to a resting position and the channel is inactivated with a hydrophobic plug over the span of 0.5-1.0 ms.
3. The inactive Na+ channel experiences a refractory period.
4. The membrane is repolarized, the channel-inactivating segment is displaced, and the gate closes over the span of several ms.
34
How does the membrane potential change after the depolarization event at the voltage-gated Na+ channel?
-60 mV -> +40 mV
35
What keeps the voltage-gated sodium channels from remaining open indefinitely? What is necessary to open the channels?
Occluded by hydrophobic amino acids within the structure of the channel; to open, must move the amino acids out of the way by changing the charge of the membrane (from negative to positive), resulting in the alpha helices changing conformation
36
What happens to a voltage-gated sodium channel when a membrane changes charge from negative to positive?
The alpha helices change conformation, resulting in the removal of the hydrophobic plug. This allows sodium ions to flood in from the outside environment.
37
How many hydrophobic plugs are there in the voltage-gated sodium channel?
two; after the first is removed, a smaller plug remains
38
What happens if the membrane potential near a voltage-gated sodium channel rapidly changes for a second time?
Due to the additional hydrophobic plug, the channel will not immediately reopen. It has a refractory period and must reset and experience another voltage change before it can open again.
39
How much time does the initial depolarization, movement of voltage-sensing alpha helices, and the opening of a voltage-gated sodium channel take?
less than 0.1 ms
40
How long does it take for the voltage-sensing alpha helices to return to a resting position while the channel is inactive?
0.5-1.0 ms
41
How long does the repolarization of a membrane, the displacement of the channel-inactivating segment, and the closure of the voltage-gated sodium channel's gate take?
several ms
42
Do voltage-gated Na+ channels depolarize or repolarize the cell?
Depolarize.
43
Do voltage-gated K+ channels depolarize or repolarize the cell?
Repolarize.
44
Do resting Na+ channels depolarize or repolarize the cell?
Resting, non-gated K+ channels maintain the baseline resting potential in animal cells, neither depolarizing nor depolarizing.
45
When the voltage-gated sodium channels open, is there a sodium influx or efflux in the cell?
Influx within 3-4 ms.
46
Why is there a loss of charge from the cell when Na+ moves in during a membrane depolarization event?
Because K+ ions move out of the cell.
47
After a membrane depolarization event due to the voltage-gated Na+ channels allowing an influx of Na+ ions, what causes the membrane potential to return to a resting state (repolarization)?
Voltage-gated K+ channels allow K+ ions to leave the cell.
48
What opens voltage-gated potassium channels?
influx of sodium as the membrane depolarizes
49
Describe the membrane potential over time as the voltage-gated channels open and close.
Starts at -60 mV, resting potential.
1. Depolarization due to influx of sodium ions after a depolarizing stimulus, raises membrane potential to +40 mV.
2. Repolarization due to the opening of the voltage-gated potassium channel that causes K+ to leave the cell.
3. The repolarization causes a hyperpolarization at -80 mV.
4. Return to resting membrane potential at -60 mV.
50
Why does the change in potential only move in one direction along the length of a cell?
Because the voltage-gated channels have refractory periods. After they've already been fired, they close, so sodium doesn't continue coming inside temporarily.
51
Which axons propagate signals most slowly, axons with small or large diameters? Why?
axons with small diameters; the speed at which a charge moves is proportional to the # of ions within the axon and axons with smaller diameters can allow in fewer ions
52
Which axons propagate signals quicker, axons with small or large diameters?
axons with larger diameters; the speed at which a charge moves is proportional to the # of ions within the axon and axons with larger diameters can allow in more ions
53
What is hyperpolarization?
when the membrane potential becomes more negative than the resting at -60 mV
54
When does hyperpolarization occur?
during the massive efflux of K+ ions after the voltage-gated K+ channel opens
55
To get our neuronal activity to occur normally, we'd need to increase the diameter of the axons by 10,000 fold. How does the human body compensate?
The axon is wrapped in a myelin sheath, which prevents the loss of charge at specific areas of the membrane by blocking the membrane from the external environment while allowing K+ ions to be released. This maintenance allows a high positive charge to remain in the axon, allowing the charge to make it to the next voltage-gated sodium channel and open it, moving from node to node.
56
What function does myelin serve?
It protects the neuron's membrane from the external environment, preventing the dilution of the high positive charge from the axon, allowing it to make it to the next voltage-gated sodium channel.
57
Where are nodes of Ranvier along the length of the axon?
Every 1 mm or 1.5 mm or so.
58
What provides the axons with myelin sheaths in the central nervous system?
Oligodendrocytes in the central nervous system
59
What provides the axons with myelin sheaths in the peripheral nervous system?
Schwann cells wrap axons
60
Describe oligodendrocytes.
Long and flat
Flat part wraps around axons, between nodes of Ranvier, to insulate
61
What are the two types of glia that wrap axons with insulating myelin?
Oligodendrocytes (CNS) and Schwann cells (PNS)
62
Where do oligodendrocytes wrap axons?
at the nodes of Ranvier; everything is covered except the nodes
63
What happens if an oligodendrocyte is defective?
1 oligodendrocyte can wrap 50-60 different axons. If defective, an axon will experience demyelination (sheath is less thick or completely unwrapped). Loss of insulation causes a dilution of the flow of ions over time and distance. Electrical signals don't propagate as well, which inhibits neural functions.
64
What causes multiple scherosis?
Permeases are secreted that destroy proteins associated with membranes of oligodendrocytes. If 1 oligodendrocyte is taken out, 50-60 axons cannot function as well.
65
Standard electrical measurement of neurons measures changes in overall cellular voltage, which reflects the opening and closing of many channels at any given time. What technique allows the measurement of ion flow through a single ion channel. How does it work?
Patch clamp electrophysiology AKA single-channel recording.
Lets you measure flow of ions and manipulate different ion concentrations.
Take a tiny tube or syringe (micropipette) and place it onto one channel. Suction causes a tight seal to form between the pipette and the plasma membrane, allowing a patch of membrane (with one or a few ion channels) to be sealed off from the surrounding medium. Allows manipulation of the current to those individual channels (in vivo or in vitro).
During the experiment, an amplifier maintains voltage across the membrane with an electronic feedback circuit, keeping the cell at a fixed membrane potential by injecting current as needed. The voltage clamp measures tiny changes in current flow from the patch pipette.
66
With respect to a typical mammalian cell, where is the highest concentration of Na+, K+, and Ca2+ found? Intracellular or Extracellular.
K+ - intracellular
Na+ and Ca2+ - extracellular
Cells have specific internal compartments that store calcium, but the majority is found extracellularly, not in the cytosol.
67
What is the difference between a chemical synapse and an electrical synapse?
A chemical synpase - nerve impulses are transmitted across the synaptic cleft via neurotransmitter
An electrical synapse - nerve impulses are transmitted seamlessly via gap junctions (pre and post-synaptic cells are closer together)
68
How does botulinum toxin (BoTox) induce localized paralysis?
Botox prevents the fusion of neurosecretory vesicles via SNARES. This prevents the release of neurotransmitters (acetylcholine), which prevents an action potential, which prevents muscle contraction.
69
What does Botox do to receptors of neurons?
Once internalized, the reducing environment inside the endosome cleaves the disulfide bond between the two chains, allowing the light chain to enter the cytoplasm. The light chain, now in an activated form, can interact with proteins found in the presynaptic nerve terminal. The catalytic light chain of each of the various toxins cleaves the v- and t-SNARE proteins. The cleavage of one or more of these proteins means that the machinery necessary for vesicle fusion is no longer present. This results in inhibition of acetylcholine release into the synaptic cleft. If the neuron innervates a muscle, prevention of acetylcholine release in turn blocks muscle contraction.
70
What are neurons?
Cells in the nervous system that send or receive electrical impulses
71
What are dendrites?
extensions to neurons that receive signals and combine them with signals received from other neurons
72
What are axons?
extensions to neurons that conduct signals, sometimes over long distances
73
What are nodes of Ranvier?
regions of axons where action potentials are renewed during propagation of mammalian cells; spaced 1-2 mm apart, not wrapped by myelin sheath
74
What are synpatic boutons? What do they do?
Ends of the branches of axons that transmit the signal to the next cell
75
What is voltage/electrical potential?
Local charge separation (one region of a solution has more positive charges and another region has more negative charges) due to work (although solutions have overall electroneutrality).
76
Which three things maintain negative steady-state ion concentrations in the cell?
1. Leak channels
2. Na+/K+ pump, which maintains low resting Na+ levels
3. Impermeable, negatively charged macromolecules, which remain inside the cell
77
How do leak channels work?
Ion channels are always open (not gated), so ions diffuse in or out depending on the membrane voltage and local ion concentration.
78
How does the Na+/K+ pump contribute to the negative resting potential of a cell?
By moving 3 sodium ions per every 2 potassium ions it allows inside. This provides the large potassium ion gradient across the membrane. This, combined with the non-moving negatively charged macromolecules, allows the inside of the cell to remain negative.
79
What is an electrochemical equilibrium?
when the force of attraction due to the membrane potential balances the tendency of ions to diffuse down their concentration gradients; when the chemical gradient is balanced with an electrical potential
80
How are voltage-gated potassium and sodium channels structurally different? How are they similar?
Voltage-gated potassium channels are multimeric - have four separate protein subunits that form a central pore in the membrane
Voltage-gated sodium channels are monomeric proteins (single large polypeptide) with four separate domains
Each domain in the sodium channel is similar to one of the subunits of the potassium channel.
In both kinds of channels, each subunit or domain contains 6 transmembrane alpha helices.
81
Why are potassium channels so specific to potassium? Why can't they also accept sodium?
Oxygen atoms in amino acids lining the center of the channel are positioned as selectivity filters, forcing potassium to give up waters of hydration. Because Na+ is smaller than K+, it can only interact with oxygen atoms on one side of the channel. It is energetically unfavorable for Na+ to give up waters of hydration and enter the channel.
82
What is conductance?
an indirect measure of the permeability of a channel when a specified voltage is applied across the membrane
83
What is channel gating?
ability of protein channels to open rapidly in response to some stimulus and close again
84
How does the voltage-gated sodium channel sense changes in voltage?
Using a voltage sensor, one of the transmembrane alpha helices
85
What is channel inactivation? What causes it?
When a channel is inactivated, it cannot reopen immediately, even if stimulated to do so.
Caused by the inactivating particle in the opening of a channel.
86
When do voltage-gated sodium channels become active again?
when the membrane potential becomes negative
87
What is the threshold potential?
created by depolarization above the resting potential; above which, the nerve cell membrane undergoes rapid alterations to electrical properties and permeability to ions, initiating the action potential
88
What is an action potential? What causes it? What happens after?
brief, but large electrical depolarization and repolarization of the neuronal plasma membrane, caused by the influx of Na+ and the subsequent efflux of K+
after initiated in one region, the action potential travels along the membrane away from the site of origin in one direction (propagation)
89
What are subthreshold depolarizations?
levels of depolarization too small to produce an action potential; when a membrane is depolarized by a small amount, the membrane potential recovers without generating an action potential
90
What is the absolute refractory period?
interval after an action potential when it's impossible to trigger a new action potential; sodium channels are inactivated and cannot be opened by depolarization
91
What is the relative refractory period? When and why does it occur?
Because both potassium leak channels and voltage-gated potassium channels are open during hyperpolarization, dragging the membrane potential far below the threshold for triggering another round of sodium channel opening.
92
What is the difference between the passive spread of depolarization and the active propagation of an action potential?
Passive spread is when depolarization travels to adjacent regions, but decreases in magnitude, making it difficul to travel far from the origin.
Propagation is the active generation from point to point along a membrane.
93
What are the points of contact between neurons?
Synaptic boutons of the axons of a transmitting neuron and the dendrites of a receiving neuron
94
How do action potential move due to myelination of axons?
They jump from node to node instead of via a steady ripple along the membrane.
95
Describe an electrical synapse.
The presynaptic neuron is connected to the postsynaptic neuron via gap junctions. As ions move back and forth between the two cells, the depolarization in one cell spreads passively to the connected cell.
96
Describe a chemical synapse.
The presynaptic and postsynaptic neurons are connected by cell adhesion proteins (NOT gap junctions). The pre and post-synaptic membranes are divided by the synaptic cleft (20-50 nm).
97
How is an electrical impulse carried across the synaptic cleft?
The electrical signal must be converted at the presynaptic neuron to a chemical signal carried by a neurotransmitter.
98
Where are neurotransmitter molecules stored?
synaptic boutons of the presynaptic neuron
99
How do neurotransmitters work?
An action potential causes the neurotransmitter to be secreted into and diffuse across the synaptic cleft. The neurotransmitter molecules bind to receptors (ligand-gated ion channel) in the postsynaptic neuron and are converted back into electrical signals. This either stimulates or inhibits the production of an action potential in the postsynaptic neuron.
100
What is a neurotransmittor?
any signaling molecule released by a neuron
101
Which neurotransmitter is used for synapses between neurons outside the central nervous system?
acetylcholine
