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Bio.590-5.Membranes

Integrative Physiology Ch. 5 - Membrane Dynamics

QuestionAnswer
Law of mass balance If the amount of a substance in the body is to remain constant, any gain must be offset by an equal loss
Law of mass balance summarized by an equation Total amount (or load) of a substance x in the body = intake + production – excretion – metabolism
Excretion The elimination of material from the body, usually taking place through the urine, feces, lungs, or skin
Clearance The rate at which a molecule disappears from the body by excretion, metabolism, or both.
The major organs involved in clearing materials Kidney and liver. But the skin, lungs, and every other organ also play a role
How does the liver clear materials from the body? Hepatocytes (liver cells) metabolize many different types of molecules, including hormones and drugs. The resulting metabolites are secreted into the intestine for excretion in the feces or into the blood for excretion by the kidneys
Note: noninvasive test to detect chronic stress Since cortisol is excreted through the salivary glands, you can test saliva for cortisol concentration
Note: what did an analysis of a sample of Napoleon’s hair show after he died? A high level of arsenic, indicating he was either murdered, poisoned accidentally, or had stomach cancer
Note: how is ethanol cleared It’s cleared by the lungs. That is the basis of the breathalyzer test. That also explains the smell emitted from alcoholics
A direct way to measure clearance as well as production, intake, movement, etc. of materials in the body Mass flow: mass flow = concentration (amount x / vol) * volume flow (vol / min)
When physiologists talk about homeostasis, what are they usually referring to? Why? They’re usually referring to the stability of the body’s internal environment, that is, the ECF which is the blood plasma and interstitial fluid. Why? Because it’s easy to monitor. ICF homeostasis is harder to monitor
Review: ECF vs. ICF ECF = extracellular fluid compartment; ICF = intracellular fluid compartment
Dynamic disequilibrium between the ECF and ICF of the body The concentrations within each are different from each other and thus create concentration gradients. This state is called dynamic disequilibrium
What is the only molecule that moves freely between cells and the ECF? Water
Osmotic equilibrium The state where the total amount of solute per volume of fluid is equal on both sides of the membrane. Because of the free movement of water, osmotic equilibrium is reached even though chemical disequilibrium exists
Chemical disequilibrium Certain solutes are more concentrated in one compartment of the body than the other
Some ions that are more concentrated in the ECF than ICF Na+, Cl-, Ca^2+, and HCO3-
Some ions that are more concentrated in the ICF than ECF K+
Are the two compartments of the ECF at chemical equilibrium with each other? No, the plasma and interstitial fluid are at chemical disequilibrium. E.g. partially because large anions can’t cross the epithelium
What happens to chemical disequilibrium when a cell dies? It returns to a state of randomness and loses its chemical disequilibrium
When K+ leaks out of a cell and Na+ leaks into a cell, what occurs The cell has to utilize energy (e.g. using the enzyme Na+-K+-ATPase) to return to a state of chemical disequilibrium
Although the overall electrical charge of the body is neutral, what does the ionic imbalance in the body result in? An electrical disequilibrium, and changes in this creates electrical signals
Is homeostasis the same as equilibrium? Evidently not. In fact, homeostasis in the context of the human body is to keep it in a state of chemical and electrical disequilibrium while maintaining osmotic equilibrium. The goal is to maintain dynamic steady states
Dynamic steady states The two disequilibria and osmotic equilibrium in the body are in dynamic steady states, that is: they’re constantly moving back and forth with no net change in the disequilibria.
Bulk flow The most general form of biological transport. It is the movement of fluid driven by a pressure gradient (from higher pressure to lower pressure). E.g. blood flowing due to the heart pumping
Other transport mechanisms aside from bulk flow Diffusion, protein-mediated transport, vesicular transport, and osmosis
Cell membranes are selectively permeable, meaning The lipid and protein composition of a given cell membrane determines which molecules will enter and which will leave
If a membrane allows a substance to pass through it, the membrane is said to be _____ to that substance. If it doesn’t allow a substance to pass it is said to be _____ to that substance Permeable; impermeable.
Molecules that enter and leave cells easily O2, CO2, and lipids
Molecules that don’t enter and leave cells easily (may not enter at all) Ions, most polar molecules, and very large molecules, e.g. proteins
Two properties influence a molecule’s movement across cell membranes: … Explain. The size of the molecule and its lipid solubility. Very small molecules and those that are lipid soluble can cross through the phospholipid bilayer. Larger and lipophobic molecules cannot
Passive transport Does not require the input of energy
Active transport Requires the input of energy from some outside source, such as the high energy phosphate bond of ATP
Diffusion The movement of molecules from an area of higher concentration to an area of lower concentration. Substances move DOWN their *chemical gradient*. Passive transport.
The rate of diffusion depends on The magnitude of the concentration gradient
Einstein’s observation about diffusion The time required for a molecule to diffuse from point A to point B is proportional to the square of the distance from A to B. If the distance doubles, the time increases from 1^2 to 2^2
How is diffusion and temperature related They’re directly related.
How is diffusion related to molecule size? They are inversely related. This is due to friction. Einstein: rate of diffusion is inversely proportional to the radius of the molecule
Do ions move by diffusion? NO. Even though the vernacular states “ions diffuse from A to B”, they’re really not. Diffusion is random molecular movement down a concentration gradient. Ions move down an electrochemical gradient.
Electrochemical gradient The combination of an electrical and concentration gradient
Substances that are hydrophilic (and hence polar) and dissolve in water are lipophilic or lipophobic? Lipophobic. Thus they cannot diffuse across the cell membrane
Simple diffusion Diffusion of lipophilic molecules that cross directly through the cell membrane
The rate and ability of simple diffusion of a molecule depends on… …the ability of the diffusion molecule to dissolve in the lipid layer of the membrane. I.e. it depends on how permeable the membrane is to the substance
Which molecules are able to cross the cell membrane by simple diffusion? Lipids, steroids, and small lipophilic molecules.
Why is water able to cross the cell membrane by diffusion even though it’s polar? Because it’s so small it squeezes through. It doesn’t cross as easily though as the simple diffusion molecules. In membranes with a lot of cholesterol, for example, they are less permeable to water
The rate of simple diffusion across a membrane is directly proportional to… …the surface area of the membrane. In other words, the greater the surface area, the more molecules can diffuse across per unit of time
The rate of simple diffusion across a membrane is inversely proportional to… The thickness of the membrane.
Fick’s law of diffusion Rate of diffusion (is proportional to) [(surface area)*(concentration gradient)*(membrane permeability)]/(membrane thickness)
What’s the most complex of the four terms in Fick’s law and why? Membrane permeability because several factors influence it: (1) the size of the diffusing molecule, (2) the lipid-solubility of the molecule, and (3) the composition of the lipid bilayer
How does cholesterol affect membrane permeability? The more cholesterol is packed into the membrane, the less permeable it becomes
What is flux? Flux is the diffusion rate per unit surface area: (diffusion rate)/(surface area)
Rearrange Fick’s law by taking out membrane thickness because it’s constant in almost all physiological systems, and define flux [(diffusion rate)/(surface area)] = (concentration gradient)*(membrane permeability)
Are the majority of the molecules in the body lipophilic and can cross cell membranes? No, they’re lipophobic or electrically charged a thus require the help of proteins to cross, a process called *mediated transport*
Facilitated diffusion Mediated transport that’s passive as molecules move down their concentration gradient, and stops at equilibrium. This is known as facilitated diffusion. It can be done by means of channel or carrier proteins
Active transport If protein-mediated transport requires ATP or another outside source of energy and moves a substance against its concentration gradient, it is known as active transport
Protein-mediated transport across a membrane is carried out by membrane-spanning proteins known as… …transporters
The four broad categories of membrane proteins: (1) structural proteins, (2) enzymes, (3) receptors, and (4) transporters
Membrane structural proteins Three roles: (1) connect membrane to cytoskeleton to maintain shape, (2) create cell junctions to hold adjacent cells together, and (3) attach cells to the matrix by linking cytoskeleton fibers to matrix collagen or other fibers
Membrane enzymes Membrane enzymes catalyze chemical reactions that take place either on the surface or just inside the cell. E.g. transferring signals from extracellular environment to the cytoplasm
Membrane receptor proteins Part of the body’s chemical signaling system. The binding of the receptor to a ligand usually triggers another event at the membrane, such as activation of an enzyme. Important in some forms of vesicular transport
Transporters They move molecules across membranes. They can be further subdivided into two categories: channel proteins and carrier proteins.
Channel proteins They create water-filled passage ways that directly link the intracellular and extracellular compartments. They’re limited to moving small ions and water.
Carrier proteins They bind to substrates that they carry but never form a direct connection between the intracellular fluid and extracellular fluid. They can change conformation. They can move larger molecules than channels can.
What are the water channels that most cells have comprised of? A protein called aquaporin
How many kinds of ion channels are there? Why are there so many? Over 100. There are a lot because many of them are specific to only certain ions (e.g. K+ or Na+ channels) or sizes/charges of ions (e.g. monovalent “one charge” channels).
What determines the selectivity of a channel? The diameter of its central pore and by the electrical charge of the amino acids that line the channel
If the amino acids in a channel are positively charged then… …negative ions will be attracted to it and pass through, while positively charged ions will be repelled
Open channels, AKA leak channels or pores Channel proteins that spend most of their time with their gate open, allowing ions to move back and forth across the membrane without regulation. They may occasionally flicker closed, but mostly stay open
Gated channels (types?) Spend most of their time in a closed state, which allows these channels to regulate the movement of ions through them. Types: chemically gated, voltage-gated, and mechanically gated channels
Chemically gated channels The gating is controlled by intracellular messenger molecules or extracellular ligands that bind to the channel protein.
Voltage-gated channels Open and close when the electrical state of the cell changes
Mechanically gated channels Respond to physical forces such as increased temperature or pressure that puts tension on the membrane and pops open the channel gate.
Three types of carrier proteins Uniport carriers, symport carriers, and antiport carriers
Uniport carriers Carrier proteins that can move only one kind of molecule.
Cotransporters A carrier protein that can move more than one kind of molecule at one time. Cotransporters include symport and antiport carriers
Symport carriers If the multiple molecules are moving across the membrane in the same direction, the carrier proteins are symport carriers
Antiport carriers If the multiple molecules are moving across the membrane in the opposite direction, the carrier proteins are known as antiport carriers
How fast can molecules move across carrier proteins compared to channel proteins Much slower because carrier proteins are very large and require a time-consuming conformational change to shuttle molecules across
Steps in the movement of a molecule through a carrier protein (1) Passage is open to one side and the molecule enters; (2) transition state with both gates closed and the molecule inside; (3) gate opens on the other side with the gate close on the side it initially entered
Examples of molecules that enter and leave cells via facilitated diffusion Sugars and amino acids
GLUT transporters Carrier proteins that move glucose and related hexose sugars across membranes
When does facilitated diffusion stop? [molecule]_ECF = [molecule]_ICF. No different from simple diffusion
How does the uptake of sugars work via GLUT transporters? Facilitated diffusion brings the sugars into the cell along their concentration gradient, through the GLUT transporter. Diffusion never reaches equilibrium however because the glucose molecules are immediately phosphorylated
What happens to the glucose molecules after they’re phosphorylated by ATP upon entering the cell? They become glucose 6-phosphate and are either sent into glycolysis or stored as glycogen. Important note: this keeps glucose concentrations low in ICF and maintains disequilibrium
Active transport creates a state of… …disequilibrium by moving molecules against their concentration gradients
Two types of active transport Primary (direct) active transport and Secondary (indirect) active transport
Primary (direct) active transport The energy to push molecules against their concentration gradient comes directly from ATP
Secondary (indirect) active transport Uses potential energy stored in the concentration gradient of one molecule to push another molecule against its concentration gradient
The only different between carrier proteins in facilitated diffusion and carrier proteins in active transport The conformation change of the protein requires the input of energy in active transport
The most important transport protein in animal cells Na+-K+-ATPase, AKA the sodium-potassium pump. It maintains the concentration gradients of Na+ and K+ across the cell membrane
The sodium-potassium pump – how does it work? The transporter is arranged so that it pumps 3 Na+ out of the cell and 2 K+ into the cell for each ATP consumed: 3 Na+ binds on ICF side, ATP is consumed, and conformation change shoots Na into ECF. 2 K+ bind and enter
Why is the K+ and Na+ disequilibrium important? The gradients are used to drive a lot of other important reactions. E.g. neural cells use the Na+ gradient to transport signals, epithelial cells use it to drive the uptake of nutrients
Review: membrane transporters that use potential energy stored in concentration gradients to move molecules are called… …secondary active transporters
How does the Na+-glucose secondary active transporter (SGLT) work? Both Na+ and glucose bind to SGLT on the ECF side. Na+ binds first causing a conformational change where the protein now has a high affinity for glucose. When glucose binds, it changes and opens to ICF
Once SGLT opens to the ICF side, what causes glucose to become dislodged? Na+ first dislodges as it moves down its concentration gradient into the cell. Then a conformational change occurs making the protein have a low affinity for glucose and glucose dislodges
Difference in direction of movement for SGLT and GLUT transporters SGLT can only move glucose one direction: into the cell because that’s the direction of the Na+’s gradient. GLUT can move either way depending on what the concentrations of glucose are inside and outside the cell
Both passive and active forms of carrier-mediated transport demonstrate three properties: Specificity, competition, and saturation
Specificity A carrier can only move one molecule or a group of closely related molecules. E.g. GLUT transporters can only move hexoses
Competition A transporter may mover several members of a related group of substrates, but those substrates will compete with one another for the binding sites on the transporter
Competitive inhibitor A competing molecule that is not transported but just blocks the transport of another molecule
Saturation The point at which all carrier binding sites are filled with substrate. At this point the cell has reached its *transport maximum* regardless of the concentration of substrate
What happens to the many macromolecules that are too large to enter or leave cells through protein channels and carriers? By means of vesicular transport
Two basic vesicular transport processes Phagocytosis and endocytosis
Phagocytosis The actin-mediated process by which a cell engulfs a bacterium or other particle into a large membrane-bound vesicle called a *phagosome*. The phagosome then pinches off from the cell membrane and fuses with a lysosome
Does phagocytosis require energy? Yes, from ATP for the movement of the cytoskeleton and for the intracellular transport of the vesicles
How does phagocytosis occur in the human body? It occurs only in certain types of white blood cells called phagocytes which specialize in phagocytizing bacteria and other foreign particles
Endocytosis: how is it different from phagocytosis? Phagocytosis protrudes out while endocytosis indents. Endo also produces much smaller vesicles. Endo is also constitutive; it’s an essential feature of cells and is always taking place. Phagocytosis is only triggered
Pinocytosis vs. selective Endocytosis can be either selective or nonselective. The nonselective version allows extracellular fluid to enter, a process called pinocytosis. Endo can also be selective, allowing only certain molecules to enter the cell
Two types of endocytosis require a ligand to bind to a membrane receptor protein: Receptor-mediated endocytosis and potocytosis
Where does receptor-mediated endocytosis take place? It takes place in coated pits, indentations where the cytoplasmic side of the membrane has high concentrations of a protein. The most common protein found in coated pits is clathrin.
Receptor-mediated endocytosis: (1) Extracellular ligands that will be brought into the cell bind to their membrane receptors.
Receptor-mediated endocytosis: (2) The receptor-ligand complex migrates along the cell surface until it encounters a coated pit.
Receptor-mediated endocytosis: (3) Once the complex is in the coated pit, the membrane draws inward, or *invaginates*
Receptor-mediated endocytosis: (4) The invaginated portion of the membrane containing the receptor-ligand complex pinches off from the cell membrane and becomes a cytoplasmic vesicle. The coated clathrin molecules are released and recycled
Receptor-mediated endocytosis: (5) In the vesicle, the ligand and the receptor separate, leaving the ligand inside and *endosome*
Receptor-mediated endocytosis: (6) The endosome moves to a lysosome if the ligand is to be destroyed, or to the Golgi if it is to be processed
What happens to the ligand’s receptors? Membrane recycling (via exocytosis): (7) The vesicle with the receptors moves to the membrane and fuses with it
What happens to the ligand’s receptors? Membrane recycling (via exocytosis): (8) The vesicle membrane is then incorporated back into the cell membrane by exocytosis and the receptors are now back on the cell surface
What kinds of materials are transported into the cell via receptor-mediated endocytosis? Protein hormones, growth factors, antibodies, plasma proteins that serve as carriers for iron and cholesterol, and more.
Note: what causes hypercholesterolemia? It’s a genetic defect that decreases the number of LDL receptors for receptor-mediated endocytosis of LDL cholesterol. As a result LDL cholesterol remains in the plasma and may accumulate in the arteries
Potocytosis A form of endocytosis that uses *caveolae* (little caves) rather than clathrin coated pits to bring receptor-bound molecules into the cell.
Caveolae Membrane regions with lipid rafts, membrane receptor proteins, and a coat of proteins name caveolins. The receptors in caveolae are lipid-anchored proteins.
Functions of caveolae To concentrate and internalize small molecules, to help in the transfer of macromolecules across the capillary endothelium, and to participate in cell signaling
Disease state related to abnormalities in caveolin Muscular dystrophy
Exocytosis The opposite of endocytosis. Intracellular vesicles move to the cell membrane, fuse with it, and then release their contents into the extracellular fluid.
Cells use exocytosis to… …export large lipophobic molecules, such as proteins synthesized by the cell, and to get rid of wastes left in lysosomes from intracellular digestion
Exocytosis involves two families of proteins: Rabs, which help vesicles dock onto the membrane, and SNAREs, which facilitate membrane fusion.
Summarize the steps in exocytosis The process begins with an increase in ICF Ca^2+ which act as a signal. Ca^2+ interacts with a calcium-sensing protein, which in turn initiates secretory vesicle docking and fusion. The vesicle membrane becomes the cell membrane
Is exocytosis a constitutive process? In some cells it occurs continuously and is thus a constitutive process, e.g. the constant release of collagen by fibroblasts via exocytosis, or cells that insert proteins onto their surface
Epithelial transport as compared to transport over a single membrane Epithelial transport requires crossing a layer of epithelial cells that are connected to one another by adhesive junctions and tight junctions
The two poles of epithelia Tight junctions separate the cell membrane into two poles: The surface that faces the lumen of an organ, called the apical membrane, and the side that faces the ECF, called the basolateral membrane.
Common physical property of the apical membrane It’s often folded into microvilli that increase its surface area
Two common terms for the apical and basolateral membranes Apical = mucosal membrane. Basolateral = serosal membrane
Transporting epithelial cells are said to be… …polarized because their apical and basolateral membranes have very different properties. E.g. certain transport proteins like the sodium-potassium pump are only found on the basolateral membrane.
Why are the epithelial cells polarized? It allows for one-way transporting of molecules
Transporting material from the lumen of an organ to the ECF is called _____; transporting material from the ECF to the lumen is called _____ Absorption; secretion
Two types of epithelial transport Paracellular transport: materials move through the junctions or between adjacent cells. Transcellular transport: materials move through the epithelial cells themselves
How does paracellular transport work? Some junctional proteins such as claudins can form large holes or pores that allow water, ions, and a few small uncharged solutes to move by the paracellular pathway.
Summary of transcellular transport Usually a two-step process. One “uphill”, which requires energy, and the other “downhill”, which is passive.
How can epithelial cells alter their membrane permeability? Selectively inserting or withdrawing membrane proteins. E.g. take out transporters and store them for later or destroy them
Transcellular transport glucose example: (1) Na+-glucose symporter (SGLT) brings glucose into cell from lumen on the apical side against its gradient using energy stored in the Na+ concentration gradient
Transcellular transport glucose example: (2) GLUT transporter transports glucose to ECF on the basolateral side by facilitated diffusion
Transcellular transport glucose example: (3) Sodium-potassium pump pumps Na+ out of the cell (using ATP), keeping ICF Na+ concentration low
Transcytosis A combination of endocytosis and exocytosis whereby a molecule enters one side of the epithelium (via receptor-mediated endocytosis or potocytosis), undergoes vesicular transport, then exits the other (via exocytosis).
Transcytosis makes it possible for… …large proteins to move across epithelium and remain intact. E.g. it is the means by which infants absorb maternal antibodies from breast milk: they’re absorbed on the apical membrane of the intestine and released to the ECF
Vesicular transport Vesicle attaches to microtubules of the cell’s cytoskeleton and is transported across the cell by motor proteins
Women have less water per kilogram of body mass than men because… …women have more adipose tissue
Because women and older people have less body water… …they will have higher concentration of a drug in the plasma than will young men if given the same dose per kilogram of body mass
Distribution of water in the body by compartment Intracellular: 65%; interstitial fluid: 25%; plasma: 10%
Osmosis The movement of water across a membrane in response to a solute concentration gradient. Water distributes itself until CONCENTRATIONS are the same (osmotic equilibrium)
How to measure osmosis? Osmotic pressure
Osmotic pressure The pressure that must be applied to a piston in compartment B to exactly oppose the osmotic movement of water into compartment B from compartment A is known as the osmotic pressure of compartment B
Units for osmotic pressure Atm or mm Hg
Osmolarity The number of particles (ions or intact molecules) per liter of solution (as opposed to molarity which is number of molecules). Osmolarity: osmol/L or OsM
To convert from molarity to OsM: (mol/L) * (#particles/molecule) = osmol/L. E.g. 1 M NaCl * 2 ions per NaCl = 2 OsM NaCl
Osmolality Concentration expressed as osmoles of solute per KILOGRAM of water. Since biological solutions are dilute and little of their weight comes from solute, the terms osmolarity and osmolality are sometimes used interchangeably
Isosmotic If two solutions contain the same number of solute particles per unit volume, we say they’re Isosmotic
Hyperosmotic If solution A has a higher osmolarity than solution B, we say solution A is hyperosmotic to solution B
Hyposmotic If solution A has a lower osmolarity than solution B, we say solution A is hyposmotic to solution B
Osmolarity is a colligative property of solutions, meaning… …it depends strictly on the number of particles per liter of solution, not on the properties of the particles
To predict the movement of water into and out of cells… …you must know the tonicity of the solution
Tonicity It’s a term to describe a solution and how it affects cell volume: it can be hypotonic, hypertonic, or isotonic
Hypotonic If a cell placed in a solution gains water and swells, we say the solution is hypotonic to the cell
Hypertonic If a cell placed in a solution loses water and shrinks, the solution is hypertonic
Isotonic The cell placed in the solution doesn’t change size thus the solution is isotonic
The osmolarity of a solution can be measured by a machine called… …an osmometer
Why can’t osmolarity predict tonicity? Because tonicity depends not only on its concentration (osmolarity) but also on the nature of the solutes in the solution (i.e. whether they can cross the membrane)
Penetrating solutes Solute particles that can enter the cell
Nonpenetrating solutes Particles that cannot cross the cell membrane
Tonicity depends on the concentration of _____ solutes only Nonpenetrating
The most important nonpenetrating solute in physiology NaCl
How can you determine the tonicity of a solution without actually putting the cell in? By knowing the relative concentrations of NONPENETRATING solutes in the cell and in the solution
If the cell has a higher concentration of nonpenetrating solutes than the solution… Water moves into the cell. The cell swells; the solution is hypotonic
If the cell has a lower concentration of nonpenetrating solutes than the solution… Water moves out of the cell. The cell shrinks; the solution is hypertonic
If the concentrations of nonpenetrating solutes are the same in the cell and solution… No net movement of water. The solution is isotonic
REVIEW AND MAKE SURE YOU UNDERSTAND FIGURE 5-28. “AN ISOSMOTIC SOLUTION IS HYPOTONIC BECAUSE CELL VOLUME INCREASED” REVIEW AND MAKE SURE YOU UNDERSTAND FIGURE 5-28. “AN ISOSMOTIC SOLUTION IS HYPOTONIC BECAUSE CELL VOLUME INCREASED”
If cells are dehydrated, what type of intravenous (IV) fluid should be used? Hypotonic
What if the situation requires fluid that remains in the ECF to replace blood loss? Isotonic IV solution should be used
Note: Normal saline solution .9% sterile aqueous solution of NaCl, (sometimes with added dextrose), to replace fluids during blood loss. Almost perfectly isotonic, it won’t swell or shrink cells
The major cation within cells; the major cation in the ECF K+; Na+
The major anions within cells; the major anions in the ECF Phosphates and negatively charged proteins; Cl-
Net charges of ICF and ECF ICF: negative; ECF: positive – hence: electrical disequilibrium
Overall, the body is electrically _____ Neutral
Conductor If separated positive and negative charges can move freely toward each other, the material through which they’re moving is a conductor
Insulator If separated charges are unable to move through the material that separates them, the material is an insulator
Examples of good conductors and insulators in the body Conductor: water. Insulator: phospholipid bilayer
Electrical gradient A difference in net charge between two regions
Electrochemical gradient The combination of electrical and chemical gradients
Resting membrane potential difference (AKA membrane potential) Resting = seen in all cells, even those “resting” idly. Potential = the gradient is a form of potential energy. Difference = there’s a difference in the amount of charge between the inside and outside of the membrane
How are electrical gradients measured in physiology: measurement convention On a relative scale rather than absolute. One side of the membrane (usually ECF) is artificially set to 0 and the other side has the opposite charge amount indicating the relative difference between the two sides
How are electrical gradients measured in physiology: equipment By means of a voltmeter which inserts electrodes (micropipettes filled with electrical conducting fluid) into both the solution (reference electrode) and cell (recording electrode) and measures the difference
The ECF in living systems is designated as the _____ and assigned a charge of _____ Ground; 0 mV
Equilibrium potential The point at which the membrane potential exactly opposes the concentration gradient of an ion
Equilibrium potential calculation Calculated by the Nernst equation: E_ion = (61/z)*log([ion]_out/[ion]_in)
Define variables from Nernst equation Z = electrical charge on ion; [ion]_in and [ion]_out = ion concentrations inside and outside the cell. E_ion is measure in mV
Can the Nernst equation work for cells that are permeable to several ions? No, then we have to use the Goldman equation which is more complex
Depolarized, repolarized, hyperpolarized When measuring changes in membrane potential, depolarized = the potential difference decreased from resting potential; repolarized = return to resting potential; hyperpolarized = potential difference has increased
Note: important to always keep in mind When the potential difference “increases” that means the charge is moving away from the ground value of zero and becoming “more negative” (hyperpolarized)
What normally causes changes from resting membrane potential? It usually changes in response to the movement of one of four ions: Na+, Ca^2+, Cl-, and K+. If a cell suddenly becomes more permeable to any of these, ions will rapidly move across the membrane
Entry of Ca^2+ or Na+ _____ the cell while the entry of Cl- _____ it Depolarizes; hyperpolarizes
If the ions must move across the membrane to alter membrane potential, wouldn’t that also affect the chemical gradient? Not really; a significant change in membrane potential requires movement of very few ions, so concentration is barely affected and the concentration gradient is virtually unchanged
How beta cells know to secrete insulin: when glucose is low When glucose is low, GLUT transporter imports less sugar, metabolism slows, less ATP is created, K_ATP stays open, K+ leaks out keeping cell at resting potential, vesicles containing insulin stay in cytosol
How beta cells know to secrete insulin: when glucose is high (note: figure 5-35, page 170 has illustration) GLUT imports more sugar, metabolism thus ATP increases, K_ATP channel closes and cell depolarizes which causes the voltage-gated Ca^2+ channel to open, this causes a signal to release insulin via exocytosis
All of the proteins in the membrane were made in… …the ER
All of the carbohydrates attached to the proteins on the membrane were added to the proteins in… …the golgi
Difference between plasma and serum They both come from the blood stream. Serum has activated clotting factors, and plasma does not. Serum is what happens after clotting. Blood transfusions will either be in the form of whole blood or plasma; not serum.
All of our blood vessels have _____ lining them Endothelium
ECF = Plasma + interstitial fluid
ICF = Intracellular fluid
How far can cells be from a blood vessel to receive the nutrients from the blood? It’s limited by diffusion: has to be within 100microns from the capillary
Two energy requirements for membrane transport Active (ATP) or passive transport
Molecules entering/leaving body must cross… …one epithelial cell, or 2 epithelial cell membranes. This is called **trans-epithelial transport**
Transepithelial transport of glucose in the kidney Na+-Glucose symporter on apical membrane brings glucose into cell against its gradient using Na+ concentration gradient. GLUT transporter on basolateral membrane transfers glucose to ECF. Na+-K+ATP pumps out Na+
Transcytosis across capillary endothelium Plasma proteins concentrated in caveolae run into the capillary endothelium where they’re taken up by endocytosis, transported across the cell (basolateral -> apical) where they’re then exocytozed.
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