1
Q
What is the fundamental structure of a biological membrane, and what are the three main types of lipids that make it up?
A
Structure: A lipid bilayer.
Lipid Components: Phospholipids, Cholesterol, and Glycolipids.
2
Q
Describe the structure of a membrane lipid and explain how they spontaneously arrange into a bilayer.
A
Lipid Structure: Amphipathic molecules with polar, hydrophilic heads and non-polar, hydrophobic tails.
Arrangement: The hydrophobic tails face inward, sticking together to avoid water, while the hydrophilic heads face outward towards the water-filled environment on both sides.
3
Q
What are the three ways proteins can be associated with the lipid bilayer?
A
Integral: Embedded within the bilayer (e.g., transmembrane proteins).
Covalently Anchored: Attached via a lipid anchor, such as a GPI anchor.
Peripheral: Loosely associated via non-covalent interactions with membrane lipids or other proteins
4
Q
What is the “Fluid Mosaic Model,” and what does it state about the movement of membrane components?
A
Definition: The model describing the membrane as a fluid bilayer with a mosaic of embedded proteins.
Movement: Both lipids and proteins are free to diffuse laterally within the membrane unless they are immobilized (e.g., by being anchored to other proteins or structures).
5
Q
What are the two key dynamic properties of biological membranes?
A
Fluidity: The membrane is not static; it is a fluid structure.
Molecular Motion: Components can move freely unless anchored or restricted.
6
Q
What are the three key structural roles of the plasma membrane that allow cells to form organized tissues?
A
Cell Junctions: Interact with neighboring cells.
Extracellular Matrix (ECM) Link: Interacts with glycoproteins in the ECM.
Cytoskeleton Linkage: Provides rigidity and shape via connections between membrane proteins and the internal cytoskeleton.
7
Q
How does the plasma membrane facilitate communication between the cell and its environment?
A
The membrane contains receptors (e.g., for neurotransmitters or hormones) that sense soluble factors outside the cell and transmit signals to the inside.
8
Q
What is the fundamental condition the plasma membrane maintains regarding ions and metabolites?
A
It maintains different concentration gradients, where ions and metabolites are concentrated much differently in the extracellular space compared to the cytoplasm.
9
Q
What is the first key function of the plasma membrane in maintaining homeostasis?
A
It acts as a barrier that prevents the unwanted diffusion of molecules down their concentration gradient from where they are more concentrated to where they are more dilute.
10
Q
What is the second key function of the plasma membrane regarding molecules and gradients?
A
It provides selective transport via membrane proteins. These proteins are necessary to actively establish and maintain the concentration gradients in the first place.
11
Q
List the three primary functions of the endoplasmic reticulum (ER).
A
Translation & Modification: Synthesis and post-translational modification of membrane/secreted proteins (Rough ER).
Lipid Synthesis: Production of lipids and steroids.
Calcium Sequestration: Especially important in muscle cells and neurons.
12
Q
What are the distinct roles of endosomes and lysosomes?
A
Endosomes: Sorting of endocytosed material.
Lysosomes: Degradation of endocytosed material and cellular waste.
13
Q
What two functions do the membranes of all these organelles share with the plasma membrane?
A
A barrier.
A means of selective transport for ions and metabolites between the organelle and the cytosol.
14
Q
Which types of molecules can diffuse directly across the lipid bilayer without assistance? Why?
A
Molecules: Small, lipophilic (non-polar) molecules.
Examples: Gases like Oxygen (O₂) and Carbon Dioxide (CO₂), and steroid hormones.
Reason: They are soluble in the hydrophobic core of the lipid bilayer and can freely diffuse.
15
Q
How are most substances that cannot diffuse directly transported across membranes?
A
Via integral membrane proteins (transport proteins) that use a variety of mechanisms to move substances from one side of the membrane to the other.
16
Q
What is exocytosis, and what are its two forms?
A
Definition: A vesicular transport process where a vesicle fuses with the plasma membrane, releasing its contents into the extracellular space.
Forms:
–Regulated Exocytosis: Occurs only in response to a specific stimulus (e.g., neurotransmitter release).
—Constitutive Exocytosis: Occurs continuously, all the time.
17
Q
What is endocytosis, and how does receptor-mediated endocytosis work?
A
Definition: The process of taking up substances from the extracellular space by invaginating the membrane to form a vesicle.
Receptor-Mediated Endocytosis:
-Substances bind to specific receptors on the plasma membrane.
-The membrane invaginates, forming a vesicle around the receptor-substance complex.
-The vesicle is translocated into the cell.
18
Q
Types of Endocytosis
A
receptor-mediated endocytosis, phagocytosis, pinocytosis.
19
Q
What are the three main classifications for movement across biological membranes?
A
Unassisted Diffusion: For small, non-polar molecules (e.g., O₂, CO₂).
Vesicular Transport: Exocytosis (out) and Endocytosis (in).
Specific Membrane Transport Proteins: Integral proteins that facilitate the movement of specific molecules.
20
Q
Why doesn’t glucose, an uncharged polar molecule, simply diffuse into the cell down its concentration gradient without help?
A
The Gradient: Glucose is highly concentrated in the extracellular space and low in the cytosol.
The Barrier: The lipid bilayer is a barrier to polar molecules. Without transport proteins, the gradient would be maintained indefinitely because glucose cannot cross on its own.
21
Q
What is the name of the process and the proteins that allow glucose to move down its concentration gradient into the cell?
A
Process: Facilitated Diffusion.
Proteins: Solute Carriers (a type of integral membrane protein that catalyze it).
Mechanism: The protein binds glucose on the extracellular side and transports it to the cytosol, moving it from high to low concentration.
22
Q
How does the rate of glucose transport change as the concentration gradient changes, and what law does this reflect?
A
High Gradient: Initially, transport velocity is high.
Shallow Gradient: As the intracellular concentration rises, the gradient becomes shallow and transport becomes less and less.
Equilibrium: When concentrations are equal, transport stops (no net transport).
Governing Law: This reflects Fick’s Law: The rate of diffusion is proportional to the concentration gradient (∆c).
23
Q
What is the sole driving force for the facilitated diffusion of an uncharged molecule like glucose?
A
Driving Force: The concentration gradient (∆c).
Energy Source: The energy driving the transport comes from the thermal motion of the molecules (passive transport). The larger the concentration difference, the higher the transport velocity.
24
Q
What is the equation for the Gibbs free energy (∆G) of transporting an uncharged molecule?
A
Equation: ∆G_c = RT ln (C_out / C_in)
Where:
R is the gas constant
T is temperature
C_out is the extracellular concentration
C_in is the intracellular concentration
Interpretation: A negative ∆G (when C_out > C_in) indicates a spontaneous process
25
Describe the setup for osmosis: the two compartments and the critical property of the membrane between them.
Compartments: One has a higher concentration of solutes (ions or uncharged molecules); the other has a lower concentration.
Membrane: It is a semi-permeable membrane, meaning it is permeable to water (via integral membrane proteins called aquaporins) but not necessarily to the solutes.
26
What is osmosis, and what are the physical consequences for the compartment with higher solute concentration?
Definition: Osmosis is the flow of water from a compartment with low solute concentration to a compartment with high solute concentration.
Consequences: In the high-solute compartment, pressure increases and, if expandable, the volume becomes larger. The volume of the lower solute decreases.
27
What happens to a cell placed in a hypotonic solution, and why?
Solution: Hypotonic (has fewer solved molecules/ions than the cytosol).
Effect on Cell: The cell swells.
Mechanism: Water rushes into the cell by osmosis. In extreme cases (e.g., a neuron in pure water), the cell will burst (lyse) as it expands beyond the plasma membrane's capacity.
28
What happens to a cell in a hypertonic solution, and what is the ideal solution for maintaining cell volume?
Hypertonic Solution: Has a higher solute concentration than the cytosol. The cell shrinks as water moves out.
Isotonic Solution: Has the same solute concentration as the cytosol. This is ideal for isolating cells as it causes no net volume change.
29
What single factor determines the osmotic pressure of a solution?
The osmotic pressure is solely determined by the number of molecules (the total concentration of solute particles) in that solution.
30
Describe the initial conditions of the two compartments before any ion movement. What is the key characteristic of each compartment's charge?
Compartment 1: High [K⁺], Low [Na⁺]. In cytosol.
Compartment 2: Low [K⁺], High [Na⁺]. In extracellular space.
Anions: Equal number in both compartments.
Net Charge: Both compartments are initially uncharged (equal cations and anions). But still have two conc. gradients.
31
What happens when potassium-specific channels open, and how does this create a membrane potential?
Ion Movement: K⁺ diffuses passively down its concentration gradient from Inside cell (high [K⁺]) to outside the cell (low [K⁺]).
Charge Separation:
Outside cells gains positive charge (more K⁺ cations than anions).
Inside cell gains negative charge (more anions than K⁺ cations).
Result: An electrical field (membrane potential) is created across the membrane.
32
What two opposing forces act on a potassium ion once the membrane potential is established?
Chemical (Concentration) Gradient: Tends to push K⁺ out of inside the cell (down its concentration gradient).
Electrical Gradient: Tends to pull the positively charged K⁺ back into the negatively charged inside the cell.
33
What is the "Equilibrium Potential" for an ion, and what is happening at this point?
Definition: The specific membrane potential at which the electrical and chemical gradients for an ion are equal in magnitude but opposite in direction.
Net Movement: At this potential, there is no net transport of the ion. A dynamic equilibrium is reached.
34
What are the equations for the free energy of the chemical (∆G_c) and electrical (∆G_e) gradients, and what is true at equilibrium?
Chemical Gradient: ∆G_c = RT ln ([X]_out / [X]_in)
Electrical Gradient: ∆G_e = zFV_m
(z = ion's charge, F = Faraday's constant, V_m = membrane potential)
At Equilibrium: The total free energy change is zero:
∆G_total = ∆G_c + ∆G_e = 0
35
What does the Nernst equation calculate, and what does this value represent biologically?
Calculates: The Equilibrium Potential (Eₓ) for a specific ion (X).
Represents: The membrane potential at which the electrochemical gradient (∆μ) for that ion is zero, resulting in no net movement of the ion across the membrane.
36
What is the general form of the Nernst equation, and what does each variable represent?
Equation: Eₓ = (RT / zF) * ln( [X]ₒ / [X]ᵢ )
Variables:
Eₓ: Equilibrium potential for ion X
R: Universal gas constant (8.314 VC K⁻¹ mol⁻¹)
T: Absolute temperature in Kelvin (K)
z: Charge of the ion (e.g., +1 for K⁺, +2 for Ca²⁺, -1 for Cl⁻)
F: Faraday constant (96,485 C mol⁻¹)
[X]ₒ: Concentration of ion X outside the cell
[X]ᵢ: Concentration of ion X inside the cell
37
What is the simplified form of the Nernst equation used at human body temperature (37°C / 310K), and how is the logarithm handled?
At 37°C (310K): Eₓ = (61.5 mV / z) * log₁₀( [X]ₒ / [X]ᵢ )
Logarithm Conversion: This simplified version uses the base-10 logarithm (log₁₀). The general form uses the natural logarithm (ln), where ln(x) = log₁₀(x) / log₁₀(e).
38
What is the value of z in the Nernst equation for potassium, calcium, and chloride ions?
Potassium (K⁺): z = +1
Calcium (Ca²⁺): z = +2
Chloride (Cl⁻): z = -1
39
What is the fundamental rule for determining the direction of net ion flow across a membrane?
Compare the actual membrane potential (Vₘ) to the ion's equilibrium potential (Eₓ).
If Vₘ < Eₓ: The ion will flow IN (if positive ion) or OUT (if negative ion).
If Vₘ > Eₓ: The ion will flow OUT (if positive) or IN (if negative).
If Vₘ = Eₓ: No net flux. The electrical and chemical gradients are balanced.
40
For potassium (E_K ≈ -91 mV), what is the net flow and why if the membrane potential (Vₘ) is -120 mV?
Vₘ (-120 mV) < E_K (-91 mV)
Net Flow: Potassium flows IN to the cell.
Reason: The membrane potential is more negative than E_K. The electrical gradient pulling the positive K⁺ ion in is stronger than the concentration gradient pushing it out.
41
What happens to potassium flow when the membrane potential (Vₘ) is exactly at its equilibrium potential (E_K)?
Vₘ = E_K
Net Flow: No net flux of potassium.
Reason: The electrical and chemical gradients are equal and opposite. K⁺ ions are driven into the cell by the electrical gradient as much as they are driven out by the concentration gradient.
42
For potassium (E_K ≈ -91 mV), what is the net flow and why if the membrane potential (Vₘ) is -60 mV?
Vₘ (-60 mV) > E_K (-91 mV)
Net Flow: Potassium flows OUT of the cell.
Reason: The membrane potential is more positive than E_K. The concentration gradient (chemical force) pushing K⁺ out is stronger than the electrical gradient pulling it in.
43
What is the fundamental difference between transport that occurs "along" an electrochemical gradient and transport that occurs "against" it?
Along the Gradient: Facilitated Diffusion. Does not require energy; movement is passive.
Against the Gradient: Active Transport. Requires energy to move substances.
44
What is primary active transport, and what is the direct source of energy used?
Definition: The direct use of energy to transport a molecule against its electrochemical gradient.
Energy Source: Hydrolysis of ATP.
Proteins Involved: ATP-dependent transporters (e.g., the sodium-potassium pump). They use the energy from breaking ATP's phosphoester bond.
45
What is the core principle behind secondary active transport?
It uses the potential energy stored in the electrochemical gradient of one molecule (e.g., Na⁺) to drive the transport of a different molecule against its own electrochemical gradient.
46
How does secondary active transport work mechanistically, and what type of protein catalyzes it?
Mechanism: As one ion (e.g., Na⁺) flows down its gradient into the cell, the released energy is used to pump another molecule (e.g., Ca²⁺ or glucose) up its gradient.
Example: Using the Na⁺ gradient to pump Ca²⁺ out of the cell.
Proteins Involved: Solute Carriers.
47
Where are ion channels found?
Present in all cells and all membranes. They are absolutely essential for generating action potentials in neurons and muscle cells (excitable cells).
48
What type of transport do ion channels facilitate, and can they perform active transport?
Mechanism: Passive transport only.
Function: They allow the facilitated diffusion of ions along (down) their electrochemical gradient.
Cannot perform active transport.
49
What is the basic structural classification of ion channels, and what is a common feature of their subunit composition?
Classification: Integral membrane proteins.
Subunits: They often consist of multiple polypeptide subunits.
50
Describe the key structural components that form the ion-conducting pathway.
Transmembrane Segments: Each subunit has multiple transmembrane segments.
The Pore: These segments line a central, narrow pore. When this pore is open, it becomes permeable to specific ions.
51
What is the name of the primary technique used to measure the tiny electrical currents flowing through ion channels?
Patch Clamp Electrophysiology
52
What specific aspect of ion channel function does patch clamp electrophysiology allow researchers to measure?
It measures the very small currents that flow through single ion channels or groups of ion channels.
53
How is patch clamp electrophysiology able to detect such small ionic currents?
The technique uses a sensitive amplifier to magnify the tiny currents, making them possible to measure and record.
54
What is the initial, crucial step common to all patch clamp configurations?
Step: A glass pipette, filled with a cytoplasm-like solution, is pressed against the cell membrane.
Action: Negative pressure (suction) is applied to form a very tight, high-resistance seal between the glass and the membrane (a "gigaseal").
55
How is a whole-cell recording established, and what does it measure?
Establishment: After forming a seal, a strong pulse of suction ruptures the membrane patch under the pipette, giving the electrode direct access to the cytoplasm.
What it Measures: The total current flowing through all the ion channels in the entire plasma membrane of the cell.
56
How is an excised patch recording established, and what is its key advantage?
Establishment: After forming a seal, the pipette is quickly retracted, ripping a small piece of membrane away from the cell.
What it Measures: Currents flowing through a very few or even single ion channels in the isolated membrane patch.
Advantage: Allows detailed study of the opening and closing properties of individual channels.
57
What is the key advantage of using the excised patch configuration?
It allows you to study single ion channels or a very few channels in isolation.
58
What specific property of ion channels can be studied in fine detail using excised patch recordings?
Channel Gating—the regulation of how a channel opens and closes.
59
Gating of ion channels:
Voltage
Extracellular ligands
Intracellular ligands
Physical stimuli
60
What is the term for the regulation of an ion channel's opening and closing?
Ion Channel Gating
61
What is the primary stimulus that opens voltage-gated channels, and name three key examples.
Stimulus: Changes in membrane potential (voltage).
Examples: Voltage-gated Sodium (Na⁺), Potassium (K⁺), and Calcium (Ca²⁺) channels.
62
Describe the basic structure of the main subunit of a voltage-gated sodium channel.
It is a polypeptide with multiple transmembrane segments.
Its structure is organized into modules (domains), each containing six transmembrane segments.
63
What is the "voltage sensor," where is it located, and what is its key property?
What & Where: It is a specific transmembrane segment within each module that is negatively charged.
Function: It responds to changes in membrane potential by physically moving.
64
How does membrane depolarization lead to the opening of a voltage-gated sodium channel?
Depolarization reduces the repulsion of the negatively charged voltage sensor.
This causes the voltage sensor to move toward the inside of the cell.
This movement triggers a conformational shift that opens the central channel pore, allowing Na⁺ ions to flow through.
65
Describe the standard voltage-clamp protocol used to study voltage-gated sodium channel (VGSC) behavior.
Hold: Keep the membrane at a negative potential (e.g., -70 mV).
Step: Quickly change the voltage to a depolarized potential (e.g., 0 mV).
Observe: That will cause the opening of voltage-gated sodium channels.
In each trial you would find that sodium channels quickly open and close again.
66
What are the three primary states of a voltage-gated sodium channel during a depolarizing step?
Closed (Resting): At negative potentials (< -55 mV). The channel is non-conducting but ready to open.
Open (Activated): Immediately upon depolarization. The channel pore is open, allowing Na⁺ to flow in.
Inactivated: After a brief period of being open, even if the depolarization continues. The channel is non-conducting and cannot re-open immediately.
67
What is activation, and how is it observed in single-channel and whole-cell recordings?
Definition: The process of the channel opening in response to membrane depolarization.
Observation:
Single-Channel: Individual channels quickly open and close.
Whole-Cell: The sum of many single-channel openings creates a large, fast, inward current.
68
What is inactivation, and why is it a distinct process from simply closing?
Definition: The process where channels close during sustained depolarization, even though the opening stimulus is still present.
Key Point: It is a distinct gated process, not just the channel closing. The channel becomes unresponsive until the membrane is repolarized.
69
How do the random openings of many single sodium channels combine to form the smooth macroscopic sodium current seen in a whole-cell recording?
When you add the currents from all trials (or all channels) together, the averaged result is a smooth, large current that rapidly activates and then inactivates, which is the classic sodium current seen in whole-cell recordings.
70
What is the basic molecular architecture of a voltage-gated ion channel?
Structure: Several transmembrane (TM) helices arranged around a central pore.
Key Feature: Some of these TM helices contain charged residues and act as voltage sensors.
71
What is the initial molecular event that occurs when the membrane depolarizes?
Event: Membrane depolarization causes the voltage sensors to physically move.
Result: This movement induces a conformational change that opens the channel pore.
72
How is the inactivated state of the channel defined at a molecular level?
Definition: The inactivated state is a stable, non-conducting conformation that is different from the original closed (resting) state.
Key Property: The channel can enter this state quickly and independently of the membrane potential (Vₘ) once it has been opened.
73
Why can't an inactivated channel re-open immediately, even if the membrane is still depolarized?
Reason: An additional conformational change is required to transition the channel from the inactivated state back to a closed (resting) state from which it can open again.
This process, called recovery, requires the membrane to be repolarized.
74
Extracellular ligands Examples
ionotropic and NT receptors
75
What is another name for many neurotransmitter receptors, and what is their fundamental function?
Name: Ligand-gated ion channels or ionotropic neurotransmitter receptors.
Function: They are ion channels whose opening is controlled by the binding of a chemical signal (a ligand, like a neurotransmitter).
76
Describe the three states of an AMPA-type glutamate receptor in response to glutamate.
Closed (Resting): In the absence of glutamate.
Open (Activated): Quickly opens upon binding glutamate, allowing ion flow.
Desensitized: Closes after a short time even though glutamate is still bound.
77
What is desensitization, and what is a key analogous process in voltage-gated channels?
Definition: The process where a ligand-gated channel closes during the continued presence of its ligand.
Analogous Process: Inactivation in voltage-gated sodium channels (closing during sustained depolarization).
78
What is the key difference between "standard" neurotransmitter receptors and channels gated by intracellular ligands?
Standard Receptors: Ligand-binding domain is in the extracellular region.
Intracellular Channels: The binding pocket for the ligand is located in the cytosolic (intracellular) domain.
79
Name three common intracellular molecules that can act as ligands to gate ion channels from the inside
Calcium (Ca²⁺)
Cyclic nucleotides (cGMP, cAMP)
ATP
80
What are the two main types of physical stimuli that can directly open ion channels?
Temperature (e.g., heat)
Mechanical Force (e.g., stretch or stress)
81
What is the mechanism and an example of a temperature-gated ion channel?
Mechanism: A rise in temperature causes a conformational change that opens the channel.
Example: TRP channels (Transient Receptor Potential channels).
82
How does mechanical force, such as stretch, open an ion channel?
Mechanism: Physical stress or stretch on the membrane or channel protein causes a conformal change, forcing the channel into an open state.
83
What are the three main categories of ion channel selectivity?
Ion-Selective: Selective for a specific ion (e.g., only sodium or only potassium).
Non-Selective Cation Channels: Conduct all cations.
Non-Selective Anion Channels: Conduct all anions.
84
What is the name of the region in the channel pore that determines which ions can pass, and what are its two key determinants of selectivity?
Name: The Selectivity Filter.
Determinants:
Charge: The charged amino acid residues lining the pore interact with passing ions.
Size: The physical diameter of the pore determines which ions are small enough to fit through.
85
How do the charged residues in the selectivity filter determine whether a channel is selective for cations or anions?
For a Cation Channel: The selectivity filter is lined with negatively charged residues that attract and stabilize positively charged cations.
For an Anion Channel: The selectivity filter is lined with positively charged residues that attract and stabilize negatively charged anions.
86
Conductance
Permeability of channel for ions
87
What is the primary structural feature of an ion channel that determines its conductance?
The size (diameter) of the channel pore.
Relationship:
A narrow pore results in low conductance (few ions pass per unit time).
A large pore results in high conductance (many ions pass per unit time).
88
Is the conductance value the same for all ion channels?
No. There is a wide variation in conductance values between different types of ion channels, largely due to differences in pore size and structure.
89
Can the conductance of a channel depend on the direction of ion flow?
Yes. For some channels, the conductance can be different depending on whether ions are flowing into the cell or out of the cell. This is due to asymmetries in the channel's structure.
90
What is Rectification?
A property where an ion channel conducts ions more easily in one direction (e.g., into the cell) than in the opposite direction (e.g., out of the cell).
91
Describe the current flow in a channel that exhibits strong inward rectification as the membrane potential changes.
At Negative Vₘ: A large inward current flows easily (ions move into the cell).
At Positive Vₘ: Little to no outward current flows (ions are blocked from moving out). The channel appears to be "closed" for outward flow.
92
What is a common molecular reason for rectification, and how is it voltage-dependent?
Reason: Channel blockade by a large, endogenous intracellular ion (e.g., a large anion like Mg²⁺ or a polyamine for potassium channels).
Voltage-Dependence:
At positive Vₘ, the blocker is attracted into and blocks the channel pore, preventing outward flow.
At negative Vₘ, the blocker is repelled from the pore, allowing inward current to pass freely.
93
What is the function of an aquaporin, and what is its basic structural similarity to an ion channel?
Function: To selectively conduct water in and out of the cell.
Structure: It is an integral membrane protein with multiple transmembrane regions that form a central pore, similar to an ion channel.
94
What does the selectivity filter in an aquaporin do, and what is it designed to exclude?
Function: It prevents molecules other than water from entering the pore.
What it Excludes:
-All ions (charged molecules).
-Any molecule that is larger than a water molecule.
95
How is the transport of water across a membrane regulated, since aquaporins are not gated?
Mechanism: By altering the number of aquaporins in the plasma membrane.
Process: A store of aquaporins in intracellular vesicles can be inserted into the membrane via vesicle fusion when more water permeability is needed.
96
What is the fundamental mechanism a solute carrier uses to move a molecule across the membrane?
Mechanism: It has a binding pocket for the solute.
Process: The binding of the solute triggers a conformational change that flips the pocket's accessibility from one side of the membrane to the other, releasing the solute. It does not have a permanent channel pore.
97
How do the transport rates of solute carriers compare to ion channels, and what determines the direction of transport?
Transport Rate: Much lower than ion channels due to the slower process of conformational changes.
Driving Force: The direction of solute flow depends entirely on the electrochemical gradient(s) of the transported molecule(s).
98
What is a uniporter, and what type of transport does it perform?
A solute carrier that transports only one species of molecule.
Type of Transport: Passive transport (facilitated diffusion). The solute flows along (down) its own electrochemical gradient.
Example: GLUT2 (Glucose Transporter 2)
99
How do some solute carriers enable active transport without using ATP directly?
Mechanism: They couple the transport of two different molecular species.
Result: This allows for secondary active transport. The energy from one solute moving down its gradient is used to power the other solute moving against its gradient.
100
What is a symporter, and how does it enable secondary active transport?
Function: Transports two different molecular species in the same direction. Co transporters
Mechanism:
One solute moves passively down its gradient.
The energy released is used to drive the secondary active transport of the other solute against its gradient.
101
What is an antiporter, and how does it enable secondary active transport?
Function: Transports two different molecular species in opposite directions. (exchangers)
Mechanism:
One solute moves passively down its gradient.
The energy released is used to drive the secondary active transport of the other solute against its gradient.
102
What is the defining characteristic of primary active transport, and what is its direct energy source?
The direct use of energy to transport a solute against its electrochemical gradient.
Energy Source: Hydrolysis of ATP.
103
Describe the two-step conformational cycle of the Na+/K+ ATPase
Cytosolic Face: 3 Na⁺ ions bind → ATP is hydrolyzed → Phosphate is transferred to the pump → Conformational change exposes the binding pocket to the outside.
Extracellular Face: 3 Na⁺ are released and 2 K⁺ ions bind → Phosphate is released → Conformational change exposes the binding pocket to the inside → 2 K⁺ are released into the cytoplasm.
104
What is the stoichiometry of the Na+/K+ ATPase, and why is its transport considered electrogenic?
Stoichiometry: For every 1 ATP hydrolyzed, it transports 3 Na⁺ out and 2 K⁺ in.
Electrogenic: Because it moves one more positive charge out than in per cycle, it directly contributes to making the inside of the cell more negative (changes the membrane potential, Vₘ).
105
How does the Na+/K+ ATPase demonstrate primary active transport for both sodium and potassium?
Sodium (Na⁺): Transported out against its strong electrochemical gradient (low inside, high outside).
Potassium (K⁺): Transported in against its concentration gradient (high inside, low outside).
106
What are four key features of ATP-dependent transporters (like the Na+/K+ ATPase)?
Perform Primary Active Transport using ATP.
Often transport multiple solutes (frequently as antiporters).
Have a fixed stoichiometry (a set number of ions moved per ATP).
Can be electrogenic, directly altering the membrane potential.
107
What are P-type ATPases, and what are two key examples?
Definition: A major class of ATP-dependent ion transporters ("ion pumps") that are phosphorylated during their transport cycle.
Examples:
Na+/K+ ATPase
Ca²⁺ ATPases (Calcium ATPases)
108
Contrast the function, location, and primary role of V-type and F-type ATPases.
V-type ATPase:
Function: Uses ATP hydrolysis to pump protons (H⁺).
Location: Membranes of intracellular vesicles (e.g., lysosomes).
Role: Acidifies the vesicle lumen, creating a pH gradient.
F-type ATPase (ATP Synthase):
Function: Uses an existing proton gradient to synthesize ATP.
Location: Inner mitochondrial membrane.
Role: Synthesizes most of the cell's ATP. It works in reverse of a pump.
109
What is the broad function of ABC transporters? Name two critical examples and their physiological or clinical significance.
Function: A diverse group that transports metabolites (cholesterol, bile acids), ions (chloride), and foreign molecules (drugs).
Examples:
Cystic Fibrosis Transmembrane Regulator (CFTR):
Transports: Chloride ions.
Defect Causes: Cystic fibrosis.
Consequence: Defective chloride and water transport, causing severe problems in secretory organs like the lungs and pancreas.
Multidrug Resistance Protein (MDR/MRP-1):
Transports: Drugs out of cells.
Clinical Issue: Cancer cells can up-regulate this protein, making them resistant to chemotherapy.
110
What are the two main structural/functional classes of ATP-dependent transporters?
ATP-dependent Ion Transporters ("Ion Pumps"):
Includes P-type, V-type, and F-type ATPases.
Primarily transport ions.
ABC (ATP-Binding Cassette) Transporters:
A very diverse group.
Transport a wide variety of molecules (cholesterol, drugs, chloride, etc.).
Classified more by structure than by a single function.
111
What does the Na+/K+ ATPase pump do, and what is its transport stoichiometry?
Function: Pumps sodium ions (Na⁺) out of the cell and potassium ions (K⁺) in.
Stoichiometry: For every 1 ATP hydrolyzed, it transports 3 Na⁺ out and 2 K⁺ in.
112
What two fundamental ion gradients does the Na+/K+ ATPase create across the plasma membrane?
Sodium (Na⁺) Gradient: High outside, low inside.
Potassium (K⁺) Gradient: High inside, low outsid
113
Why is the Na+/K+ ATPase essential for neurons and muscle cells?
It is crucial for establishing and maintaining the resting membrane potential (Vₘ).
The ion gradients it creates are necessary for excitability, allowing these cells to generate action potentials.
114
What is the primary role of the sodium gradient created by the Na+/K+ ATPase?
It is a universal energy source used to power the secondary active transport of many other molecules across the plasma membrane.
115
List three specific examples of secondary active transport processes driven by the sodium gradient.
Uptake of Amino Acids: Via symport (co-transport) with Na⁺.
Extrusion of Calcium (Ca²⁺): Via antiport (exchange) with Na⁺.
Extrusion of Protons (H⁺): Via antiport with Na⁺ to prevent cytoplasmic acidification.
116
What important gradient is established by the potassium flux from the Na+/K+ ATPase?
The high intracellular K⁺ concentration helps create a chloride (Cl⁻) gradient (high outside, low inside), often via symport of K⁺ and Cl⁻ out of the cell.
117
What is the fundamental job of calcium ATPases like PMCA and SERCA
To remove calcium (Ca²⁺) from the cytoplasm, maintaining a very low cytosolic calcium concentration.
118
Why is it critical for the cytoplasm to have such a low concentration of calcium ions?
Reason: It allows calcium to function as a potent signaling molecule.
Mechanism: Scarcity enables a rapid and large signaling pulse when calcium-permeable channels open, causing a fast influx from outside the cell or from the endoplasmic reticulum.
119
What are the two main types of calcium ATPases and where are they located?
PMCA (Plasma Membrane Ca²⁺ ATPase): Pumps calcium out of the cell.
SERCA (Sarco/Endoplasmic Reticulum Ca²⁺ ATPase): Pumps calcium into the endoplasmic/sarcoplasmic reticulum.
120
What happens to a cell if its calcium ATPases are defective?
Result: Cytosolic calcium levels rise uncontrollably.
Severe Outcome: A large increase in intracellular calcium induces cell death (apoptosis). This is especially deleterious with a defective PMCA pump.
