Midterm #3: Membrane Transport Flashcards
1
Q
3 ways in which molecules can cross membrane barriers:
A
- Diffusion: small, non-polar molecules can spontaneoulsy pass through the bilayer
- Passive Transport: larger or more polar molecules can pass through channels down a **concentration gradient. ** May be tightly regulated
- **Active transport: **solute can also be pumped by transporters against a concentration gradient, in an energy-dependent process
2
Q
Diffusion Across Membranes
A
- Very small nonpolar substance such as O2, N2, CO2 and NO can diffuse through a lipid bilayer
- The diffusion rate (“flux”) depends on:
- the **solubility **of the molecule in lipid
- the concentration gradient across the membrane
- flow continues until an equilibrium is achieved
- Larger and polar molecules cannot easily or quickly diffuse across a bilayer and their transport across biological membranes must be mediated by two types of proteins: channels and transporters
3
Q
Channels and Passive Transport
A
- Hole in membrane where it can diffuse down concentration gradient
- facilitated diffusion
- No energy (passive transport)
- Cannot establish concentration gradients
- Can be selective
- provides appropriate size and environment
- Display substrate specificity with defined Vmax and Km parameters
4
Q
Two types of channels or pores: Ungated and Gated
A
- Ungated:
- facilitated diffusion of substrates
- selective/nonselective
- Ex: Beta-barrel porins, aquaporins
- Gated or Regulated Channels
- switch between open and closed states
- highly selective (usually small charged ions)
- Regulated by: membrane potential (voltage), ligand binding, mechanical stress or phosphorylation
- Ex: Voltage Gated Na+ Channel, Voltage Dependent Ca+ Channel, GABAA Receptor, Nicotinic-Acetylcholine Receptor
5
Q
Two types of Gating for Channels
A
- Peptide Plug
- Rotational Gating
6
Q
Porins
A
- AKA: Beta Barrel Channels
- Outer membrane of gram-negative bacteria and of mitochondria
- Form aqeuous channels through membrane
- Trimers
- Each subunit forming a 16- or 18-strand membrane spanning beta barrel
- Center is lined with charged side chains and is filled with water, forming a passageway for the movement of small molecules
- Depending on the nature of the side chains, the porin may be selective for ions, amino acids, or sugar
7
Q
Aquaporins
A
- alpha-type channels
- several subunits with multiple transmembrane alpha-helices
- Very sensitive, allowing only the passage of water
- Narrow channel lined with charged residues and two specifically placed Asn residues at the center of the pore
- Important role in reabsorption of water in the kidneys, and in water transport in the roots of plants
8
Q
Voltage-Gated Sodium and Potassium Channels
A
- Diffusion of ions across membranes depends on concentration gradient and membrane potential
- called the electrochemical gradient
- In the resting state, neurons maintain a negative membrane potential with excess extracellular Na+ and intracellular K+
- Signals are transmitted along nerve cell axons in the form of action potentials mediated by Na/K voltage gated channels.
- Inital stimulus causes Na channels to open, Na flows in and depolarizes cell membrane
- K channels open and K flows out to restore membrane potential
9
Q
Name this structure
A
- Tetrodotoxin: found in certain pufferfish, inhibits voltage-gated Na+ channels and causes paralysis
10
Q
Voltage-Dependent Calcium Channels (VDCC)
A
- found in muscle cells and neurons
- closed at resting membrane potential but activated by depolarization of the membrane
- Ca+ entry into the cell, cauing contraction/excitiation
- Open in milliseconds, but stay open longer giving a more sustained action potential
11
Q
Calcium Channel Blockers
A
- Ex: amlodipine
- Treat HTN
- Inhibit VDCC in heart muscle, decreasing cardiac contractility
- Decreases cardiac output
- Inhibit VDCC in arterial smooth muscle causing increase in arterial diameter (vasodialation)
- Decreases total peripheral resistance
12
Q
Name This Structure
A
Amlodipine
13
Q
Ligand-gated Channels
A
- GABAA Receptor is a Cl- channel found in CNS
- Activation allow Cl into cell, causing hyperpolarization
- neuronal inhibition
- **Benzodiazepines **and barbituates enhance GABAAR activity.
-
Nicotinic-Acetylcholine Receptor (nAChR) is a gated channel at neuromuscular junction
- ACh binding to receptor opens the channel, enabling Na+ to enter and K+ to exit
- Local depolarization at motor end plate, initiating mucle contraction
- Acetylcholinesterase rapidly degrades ACh in the synaptic cleft
14
Q
Name this structure
A
GABA: gamma-aminobutyric acid
15
Q
Name this structure
A
acetylcholine
16
Q
nAChR inhibitors
A
- Non-depolarizing neuromusclar junction agents
- bind to nAChR and competitvely inihibit ACh binding
- Curare alkaloids like d-tubocurarine
- Muscle relaxant like **atracurium **
- Depolarizing neuromuscular junction agents
- bind to nAChR and open the channel resulting in membrane depolarization
- Mimic ACh, first causing contraction and then paralysis
- Succinylcholine is used via IV. Adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery and mechanical ventilation
17
Q
Name this structure
A
d-tubocurarine
18
Q
Name this structure
A
atracurium
19
Q
Name this structure
A
Succinylcholine
20
Q
Uniport, Symport, Antiport
A
- Uniport: moves a single substance at a time
- Symport: transports two different substances in the same direction across membrane
- Antiport: move two different substances in opposite directions across the membrane
21
Q
Transporters may also operative passively (“facilitated transport”) or actively, through two modes:
A
- Primary active transport: involves the consumption of ATP
- Secondary active transport: is coupled to an exisiting electrochemical gradient
22
Q
GLUT1
A
- passive uniporter
- transports glucose down a concentration gradient into RBC and many other tissues
23
Q
Primary Active Transport: The Na/K-ATPase
A
- Maintains the concentration of sodium (extracellular→intracellular) and potassium (intra→extra)
- Each rxn cycle hydrolyzes 1 ATP, pumps 3 Na out and 2 K in
- Excitable tissue like nerve and muscle have high Na/K ATPase activity to maintain membrane potential
- Separate Ca ATPase transporter maintains the Ca gradient for VDCC activity
- In addition, the concentration gradients can power other co-transport proteins (secondary active transporters)
- Main consumer of ATP in body at rest
24
Q
Primary Active Transport: P-Glycoprotein (P-gp)
A
- P-gp (aka: MDR1 or ABCB1) pumps a broad array of xenobiotic compounds out of cytoplasm in an ATP-dependent process.
- Key player in drug transport in gut, liver, kidney and blood-brain barrier as well as in cancer cell multidrug resistance
- Many drugs also inhibit P-gp activity, a potential source for drug-drug interaction
- P-gp inhibitors such as quinidine can substantially increase exposure to the P-gp substrate digoxin
25
Q
Secondary Active Transport
A
- Takes advantage of gradient already established by ATPase pump
- The Na-glucose transporter found in renal epithelial cells of the kidneys is a symport
- Glucose import is powered by the sodium gradient set up by the Na/K-ATPase
- The Na/Ca-exchanger (NCX) in cardiac cells is an antiport also powered by sodium gradient.
- exchanges 3 Na per Ca exported
- Much faster than Ca-ATPase but has a lower affinity
- cannot maintain as steep a concentration gradient
26
Q
Cardiac Glycosides
A
- natural products that increase the intensity of heart muscle contraction
- treat congestive heart failure
- Digoxin
- Narrow therapeutic index: 0.8-2 ng/mL, toxic is greater than 2.4 ng/mL
- Steroids that inhibit Na/K-ATPase decreasing the Na gradient
- Inhibits NCX, attenuates the rapid removal of Ca from the cell
- Increase in intracellular Ca increases the contractility of the cardiac muscle and the intensity of cardiac contraction
*
27
Q
Name this structure
A
Digoxin
