1
Q
membrane transport proteins
A
- span the lipied bilayer and provide private passageways across membrane for select substances
- works for substances that, unlike CO2 and O2, can’t diffuse across lipid bilayer
- protein-free, artificial lipid bilayers(eg liposomes) are impermeable to most water-soluble molecs b/c they don’t have transport proteins
2
Q
transporters
A
- shift small organic molecules or inorganic ions from one side of the membrane to the other by changing shape
- only transfers molecs/ions that fit specific binding sites on proteins
- transporters bind their solutes with great specificity, in the same way an enzyme binds its substrate
- gives transporters their selectivity
3
Q
channels
A
- form tiny hydrophilic pores across the membrane through which such substances can pass by diffusion
- discriminate based on size and electric charge
- when channel is open, any molec that is small enough and has correct charge goes through
- Most channels only permit passage of inorganic ions and are therefore called ion channels
- bc ions are electrically charged, their movements can create a powerful electric force/voltage across membrane
4
Q
relative ease at which polar, water-soluble solutes cross cell membranes
A
- small nonpolar molecs(O2,CO2): dissolve readily in lipid bilayers, so they rapidly diffuse across them
- allows cellular respiration to occur
- uncharged polar molecs: if small enough, diffuse readily across bilayer
- H2O and ethanol cross at a measureable rate, while glycerol crosses less quickly, and glucose(large) hardly crosses at all
- charged molecules(all inorganic ions): no matter how small, lipid bilayer is highly IMpermeable to these
- their charges and strong electric attraction to water inhibit their entry into the inner, hydrocarbon phase of the bilayer
- Thus synthetic lipid bilayers are a billion (109) times more permeable to water than they are to even small ions such as Na+ or K+.
5
Q
ion concentrations inside vs. outside a cell
A
- concs are very diff bc cell membranes are impermeable to inorganic ions
- Na+, K+, Ca2+, Cl-, H+ movement are essential in producing ATP and communicating w/ nerve cells
- Na+ is most abundant cation outside cell (NO)
- K+ most abundant inside (KI)
- cells need to be almost completely neutral in charge to avoid being ripped apart by electrical forces
- Na+ balanced by Cl-
- high conc of K+ inside is balanced by negatively charged organic and inorganic ions(eg nucleic acids, proteins, and cell metabolites)
6
Q
membrane potential
A
- occurs when a tiny excess of pos or neg charge in plasma membrane causes electrical imbalances which generate a voltage diff across the membrane
- “unstimulated” cells have almost neutral membrane
- voltage diff(resting membrane potential) is steady
- from -20~-200mV
- inside of cell is slightly more neg than outside
- This membrane potential allows cells to transport of certain metabolites and provides those cells that are excitable with a way to communicate with their neighbors
- voltage diff(resting membrane potential) is steady
7
Q
A
8
Q
passive transport
A
- Molecules will spontaneously flow “downhill” from a region of high concentration to a region of low concentration, provided a pathway exists
- passive bc they need no additional driving force
- no energy is used
- even though the solute moves in both directions across the membrane, more solute will move in than out until the two concentrations equilibrate
- ALL channels and many transporters act as conduits
Facilitated diffusion(a form of passive):
- Diffuse across membrane with help of membrane protein (no energy input)
- E.g. water by aquaporin, some ions (channels)
9
Q
active transport
A
- the movement of a solid against the concentration gradient
- carried out by special types of transporters called pumps
- pumps harness energy from either ATP hydrolysis(a transmembrane ion gradient) or sunlight
10
Q
both the concentration gradient and membrane potential influence the passive Transport of charged solutes
A
- uncharged molecs: direction is determined by conc gradient
- charged molecs: membrane potential exerts a force on the
- cytosolic side of plasma membrane is usually at a negative potential relatibe to extracellular site, so membrane potential pulls positively charged solutes into cell and push neg charged ones out
11
Q
electrochemical gradient
A
- electrochemical gradient= Concentration gradient + membrane potential
- charged solutes tend to move down conc gradients
- The net force driving a charged solute across a cell membrane is therefore a composite of two forces, one due to the concentration gradient and the other due to the membrane potential
- this net force is the solute’s electrochemical gradient
- determines direction each solute will flow by passive transport
- this net force is the solute’s electrochemical gradient
12
Q
osmosis
A
- osmosis: diffusion of water across a membrane
- aquaporins in plasma membrane help water molecs diffuse across bilayer
- osmolarity(total conc of solute particles inside cell) generally is greater than conc outside cell
- this osmotic gradient tends to pull water into cell
- this movement of water down its conc gradient is called osmosis
- if osmosis occurs w/o constraint, the cell can swell
- animal cells use their gel like cytoplasm to resist osmotic swelling
- protozoans(eg amoebae) use contractile vacuoles that discharge water to exterior
- plant cells have tough cell walls that have tugor pressure(osmotic swelling pressure) to keep cells tense
- if tugor pressure is lost, plants wilt
13
Q
glucose transporter
A
- E.g. GLUT protein family – multipass(12) a-helical bundle
- Glucose uncharged; concentration gradient only • Passive transport
- in plasma membrane of many mammals
- the protein, which consists of a polypep chain that crosses membrane 12+ times and adopts several conformations
- in 1 transformation, transporter exposes binding sites for glucose to the exterior of the cell, in another its to the interior
- bc glucose is uncharged, chemical component of its electrochemical gradient is 0.
- SO, conc gradient controls direction alone
- When glucose is plentiful outside cells(after a meal) the sugar binds to the transporter’s externally displayed binding sites; when the protein switches conformation—spontaneously and randomly—it carries the bound sugar inward and releases it into the cytosol, where the glucose concentration is low
- Conversely, when blood glucose levels are low(when you are hungry)—the hormone glucagon stimulates liver cells to produce large amounts of glucose by the breakdown of glycogen. The glucose concentration is higher inside liver cells than outside. This glucose binds to the internally displayed binding sites on the transporter. When the protein switches conformation in the opposite direction, the glucose is transported out of the cells, where it is made available for others to import
- still very selective even though passive transporters of this type play no part in determining direction
14
Q
pumps
A
- cells can’t rely solely on passive transport, so they use transmembrane pumps to actively transport as well
- transmembrane pumps: carry out active transport in 3 ways:
- 1) ATP-driven pumps
- hydrolyze ATP to drive uphill transport
- 2) Coupled pumps
- link the uphill transport of one solute across a membrane to the downhill transport of another
- 3) Light-driven pumps,
- found mainly in bacterial cells
- use energy derived from sunlight to drive uphill transport(bacteriorhodopsin)
- 1) ATP-driven pumps
15
Q
Na+ pump
A
- accounts for 30% or more of animal cells’ ATP consumption
- uses ATP hydrolysis to transport 3 Na+ out of the cells as it carries 2 K+ in
- aka Na+-K+ ATPase OR Na+K+ pump
- energy from ATP hydrolysis induces protein conformational changes that drive ion exchange(phosphate group removed from ATP gets transferred to pump itself)
- the ion transport involves a rxn cycle, in which each step must occur for the next to also occur.
- whole cycle only take 10 millisecs
- EX: ouabin inhibits pump by preventing the binding of extracellular K+, stopping the cycle
16
Q
Na+ pump generates a steep conc gradient of Na+ across the plasma membrane
A
- ceaselessly expels the Na+ that is constantly entering the cell through other transporters and ion channels in the plasma membrane
- In this way, the pump keeps the Na+ concentration in the cytosol about 10–30 times lower than in the extracellular fluid and the K+ concentration about 10–30 times higher
- creates a large electrochemical gradient
- high Na+ conc outside cell
17
Q
Ca2+ pumps keep cytosolic Ca2+ conc low
A
- less plentiful than Na+, but both have low conc in cytosol and high conc in extracellular fluid
- movement of Ca2+ across cell membranes is nonetheless crucial, because Ca2+ can bind tightly to a variety of proteins in the cell, altering their activities
- The lower the background concentration of free Ca2+ in the cytosol, the more sensitive the cell is to an increase in cytosolic Ca2+
- Ca2+ pumps are found in both ER membrane and plasma membrane
- Ca2+ pumps are ATPases that work similar to Na+
- BUT, they don’t require binding and transporting of a second ion to return to their og conformation
- they also have similar aa sequences and structures, indicating common evolutionary origin
- Ca2+ pumps are ATPases that work similar to Na+
18
Q
coupled pumps
A
- A gradient of any solute across a membrane can be used to drive the active transport of a second molecule
- In a coupled pump, the downhill movement of the first solute down its gradient provides the energy to power the uphill transport of the second
- EX:
- They can couple the movement of one inorganic ion to that of another
- an inorganic ion to that of a small organic molecule
- one small organic molecule to that of another
- Symport: moves both solutes in same direction
- Antiport: opposite directions
- Uniport: a transporter that ferries one type of solute(not coupled)
- EX: passive glucose transporter
19
Q
The electrochemical Na+ gradient drives coupled pumps in the plasma membrane of Animal cells
A
- Symports that make use of the inward flow of Na+ down its steep electrochemical gradient have an important role in driving the import of other solutes into animal cell
- If the gut epithelial cells had only this symport, however, they could never release glucose for use by the other cells of the body
- they have 2 types of glucose transporters located at opposite ends of the cell
20
Q
H+ pumps
A
- plants, bacteria, and fungi(including yeasts) don’t have Na+ pumps in their plasma membranes, but rather, they have H+ pumps that import solutes to the cell
- pump H+ out of the cell, thus setting up an electrochemical proton gradient across this membrane and creating an acid pH in the medium surrounding the cell
- controls import of many sugars and aa’s into bacterial cells
- In some photosynthetic bacteria, the H+ gradient is created by the activity of light-driven H+ pumps such as bacteriorhodopsin
- membranes of intracellular organelles(eg lysosomes of animals and central vacuole of plant/fungus): have pumps that resemble turbine like enzyme and synthesize ATP in mitochondria and chrloroplasts
- they actively transport H+ out of cytosol and into organelle, keeping pH of cytosol neutral and pH of interior of organelle acidic
21
Q
voltage-gated ion channels respond to the membrane potential
A
- Voltage-gated ion channels have domains called voltage sensors that are extremely sensitive to changes in the membrane potential: changes above a certain threshold value exert sufficient electrical force on these domains to encourage the channel to switch from its closed to its open conformation
- When one type of voltage-gated ion channel opens, the membrane potential of the cell can change
- ion channels → membrane potential → ion channels
22
Q
neuron
A
- neurons receive, integrate, and transmit singals
- neurons carry signals inward from sense organs to CNS(brain and spinal cord)
- cell body: contains nucleus and has long thin extensions raidiating out from it
- axon: one long extension which conducts electrical signals away from cell body toward distant target cells
- also has dendrites: several shorter extensions
- provide enlarged surface area to receive signals from the axons of other neurons
- each branch ends in a nerve terminal
- allows messages to be passed to many target cells simultaneously
- also has dendrites: several shorter extensions
23
Q
action potentials
A
- Neurons solve this long-distance communication problem by employing an active signaling mechanism.
- Here a local electrical stimulus of sufficient strength triggers an explosion of electrical activity in the plasma membrane that propagates rapidly along the membrane of the axon, continuously renewing itself all along the way.
- This traveling wave of electrical excitation, known as an action potential, or a nerve impulse, can carry a message, without the signal weakening, all the way from one end of a neuron to the other, at speeds of up to 100 m/s
- Excitable cells: nerve, muscle, endocrine cells
- Rapid signaling
- Switches in polarity of membrane potential
24
Q
Action potentials Are mediated by voltage-gated cation channels
A
- depolarization: When a neuron is stimulated, the membrane potential of the plasma membrane shifts to a less negative value (toward 0)
- if depolarization is sufficiently large, it causes voltage-gated Na+ channels in membrane to open
- as they open small amts of Na+ enter the cell down the gradient
- this influx of pos charge furthers depolarization, which opens more channels
- continues until(in ab 1 ms) resting value went from -60mV to +40mV
- +40mV is when the driving force for Na+ movement=0
- Na+ channels have an automatic inactivating mechanism—a special inactivated conformation, in which the channel is closed, even though the membrane is still depolarized.
- The Na+ channels remain in this inactivated state until the membrane potential has returned to its initial negative value
25
voltage gated K+ channels
* opening of K+ channels helps Na+ channel return to inactivated state
* they open in response to depolarization, but they stay open longer so they have a slower response time
* K+ rapidly flows down conc gradient out
* Highly selective for K+ (Selectivity filter made from amino acids inside channel)
* As the local depolarization reaches its peak, K+ ions start to flow out of the cell through these newly opened K+ channels down their electrochemical gradient, temporarily unhindered by the negative membrane potential that normally restrains them in the resting cell.
* The rapid outflow of K+ through the voltage-gated K+ channels brings the membrane back to its resting state much more quickly than could be achieved by K+ outflow through the K+ leak channels alone
* Once it begins, the self-amplifying depolarization of a small patch of plasma membrane quickly spreads outward: Na+ flowing in through open Na+ channels begins to depolarize the neighboring region of the membrane, which then goes through the same self-amplifying cycle
26
synapses
* signals are transmitted from nerve terminals(after action potentials reached them) to target cells at specialized junctions known as synapses
* electrical signal is converted into a chemical signal, in the form of a small, secreted signal molecule known as a neurotransmitter in order to bridge synaptic cleft
* Neurotransmitters are initially stored in the nerve terminals within membrane-enclosed synaptic vesicles
* When an action potential reaches the nerve terminal, some of the synaptic vesicles fuse with the plasma membrane, releasing their neurotransmitters into the synaptic cleft
27
voltage-gated Ca2+ channels
* When an action potential reaches the nerve terminal, some of the synaptic vesicles fuse with the plasma membrane, releasing their neurotransmitters into the synaptic cleft.
* The depolarization of the nerve-terminal plasma membrane caused by the arrival of the action potential transiently opens voltage-gated Ca2+ channels, which are concentrated in the plasma membrane of the presynaptic nerve terminal.
* Because the Ca2+ concentration outside the terminal is more than 1000 times greater than the free Ca2+ concentration in its cytosol Ca2+ rushes into the nerve terminal through the open channels
* inc in conc in cytosol triggers membrane fusion that releases neurotransmitters
28
converting the chemical signal back into an eleectrical signal
* released neurotransmitter rapidly diffuses across synaptic cleft and binds to neurotransmitter receptors in postsynaptic plasma membrane of target cell
* causes a change in the membrane potential of the target cell, which—if large enough—triggers the cell to fire an action potential
* neurotransmitter is then quickly removed from the synaptic cleft—either by enzymes that destroy it, by pumping it back into the nerve terminals that released it, or by uptake into neighboring non-neuronal cells
* rapid removal of the neurotransmitter limits the duration and spread of the signal and ensures that, when the presynaptic cell falls quiet, the postsynaptic cell will do the same
29
transmitter-gated ion channels
* rapid responses depend on transmitter-gated ion channels(a subclass of ligand-gated ion channels)
* aka ion-channel-coupled receptors
* their function is to convert the chemical signal carried by a neurotransmitter back into an electrical signal
* The channels open transiently in response to the binding of the neurotransmitter, thus changing the ion permeability of the postsynaptic membrane and in the membrane potential
* If the change is big enough, it will depolarize the postsynaptic membrane and trigger an action potential in the postsynaptic cell
* EX: neuromuscular junction—the specialized synapse formed between a motor neuron and a skeletal muscle cell. In vertebrates, the neurotransmitter here is acetylcholine, and the transmitter-gated ion channel is an acetylcholine receptor
30
excitatory neurotransmitter
* Excitatory neurotransmitters:
* chief receptors: acetylcholine and glutamate(ligand-gated cation channels)
* When a neurotransmitter binds, these channels open to allow an influx of Na+, which depolarizes the plasma membrane and thus tends to activate the postsynaptic cell, encouraging it to fire an action potential
* Encourages postsynaptic action potential
31
inhibitory neurotransmitters
* main receptors: γ-aminobutyric acid (GABA) and glycine(ligand-gated Cl– channels)
* When neurotransmitters bind, these channels open, increasing the membrane permeability to Cl–; this change in permeability inhibits the postsynaptic cell by making its plasma membrane harder to depolarize
* Make it harder for membrane depolarization
* Toxins that bind to one of these excitatory or inhibitory neurotransmitter receptors can have dramatic effects on humans
* Curare causes muscle paralysis by blocking excitatory acetylcholine receptors at the neuromuscular junction
32
psychoactive drugs
* drugs used in the treatment of insomnia, anxiety, depression, and schizophrenia act by binding to transmitter-gated ion channels in the brain
* Sedatives and tranquilizers(barbiturates, Valium, Ambien, and Restoril)bind to GABA-gated Cl– channels. Their binding makes the channels easier to open by GABA, rendering the neuron more sensitive to GABA’s inhibitory action.
* By contrast, the antidepressant Prozac blocks the Na+-driven symport responsible for the reuptake of the excitatory neurotransmitter serotonin, increasing the amount of serotonin available in the synapses that use it
33
The complexity of synaptic signaling enables us to Think, Act, learn, and remember
* Why would evolution have favored such an apparently inefficient and vulnerable way to pass a signal between cells?
* consider how synapses function in the context of the nervous system
* To carry out complex functions, neurons have to do more than merely generate and relay signals: they must also combine them, interpret them, and record them. Chemical synapses make these activities possible
34
synaptic plasticity
* **synaptic plasticity**: a synapse can also adjust the magnitude of its response—reacting more/less vigorously to an incoming action potential—based on how heavily that synapse has been used in the past
* How much neurotransmitter released
* Postsynaptic response changes
* Can last from hrs-weeks, or longer
* triggered by the entry of Ca2+ through special cation channels in the postsynaptic plasma membrane
* synapses learn!
35
optogenetics
* using light to control neurons into which channelrhodopsin—or any other light-gated channel—has been introduced by genetic engineering techniques
* mice sex
* As genetic studies continue to identify genes associated with various human neurological and psychiatric disorders, the ability to exploit lightgated ion channels to study where and how these genes function in model organisms promises to greatly advance our understanding of the molecular and cellular basis of human behavior
* Optogenetics Uses Light-Gated Ion Channels To Stimulate Neurons
36
tonicity
* Hypotonic: outside conc \< inside(cell) conc
* lyses red blood cells(H2O in)(they explode)
* turgid(normal plant cells)
* Isotonic: outside = inside
* flaccid plant cells
* Hypertonic: outside \> inside
* hyper --\> greater
* shrivels red blood cells(H2O out)
* shriveled(plasmolyzed) plant cells
37
exocytosis
* materials are secreted out of the cell
38
endocytosis
* materials are brought into the cell
* Phagocytosis(cellular eating)
* Pinocytosis(cellular drinking)
* Receptor-mediated endocytosis
39
Mechanically gated ion channels
* Mechanically-Gated Ion Channels In Ear Respond to Vibrations
* Voltage-and Mechanical Gated Channels Coordinate Touch Response in Mimosa Pucida
* plants remember you if you mess with them enough
40
Na+ K+ pump
* pumps out Na+
* helps return membrane to resting potential(just like voltage gated K+ channels)
Bio Core I
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