Chapter 6 Flashcards
Aquaporins are involved in
a. thirst mechanism
b. concentration of urine by kidneys
c. digestion
d. regulation of body temp
e. secretion and absorption of spinal fluid
f. secretion of tears, saliva, sweat, and bile
g. reproduction
Structure of aquaporins
a. Homotetramers
b. each subunit forms a pore
What are the three features that confer the water-specificity of aquaporin?
a. size restriction via a constriction region
b. electrostatic repulsion
c. water dipole orientation
In kidneys, what does the aquaporin-1 type protein channels do?
Help concentrate 180 liters of blood filtrate per day into a urine volume of 1.5 liters per day by reabsorbing
Where does the aquaporin-1 have a constitutive high water permeability?
In the epithelial cells of the proximal convoluted tubules and descending thin limbs of the loop of Henle
Vasopressin stimulates the expression of
Aquaporin-2
What does the stimulation of the expression of aquaporin-2 result in?
Increased urine concentration
Where is the aquaporin-2 expressed?
In the collecting ducts
What are the steps of action potential?
- opening of voltage-gated Na+ channels
- rapid flow of Na+ ions into the cell
- membrane depolarization
- depolarization stops within milliseconds, Na+ channels rapidly inactivate
- early repolarization begins, voltage-gated Ca2+ channels open
- transient outward K+ currents balance the Ca2+ channels
- more K+ ions rapidly exit the cell
- repolarization
- Na+/K+ - ATPase drives membrane potential toward repolarization to reestablish the resting negative membrane potential
What happens when depolarization stops?
Na+ channels rapidly inactivate
What happens when early repolarization begin?
voltage-gated Ca2+ channels open
What results after the K+ ions rapidly exit the cell?
repolarization
Ca2+ signaling regulates what?
muscle contraction and heart rhythm
Excitation-concentration coupling
Process in which membrane depolarization results in production of force by muscles (cardiac and skeletal)
What cell has much lower [Ca2+] compared to the extracellular or ER/SR concentrations?
Resting cells
Resting cells have much lower [Ca2+] compared to where?
the extracellular or ER/SR concentrations
When is the signal initiated at the plasma membrane?
when it is depolarized from an incoming action potential
What are the 4 steps of excitation-contraction coupling?
- Depolarization activates Ca2+ channels
- Ca2+ influx stimulates Ca2+ release from SR into cytosol
- Increased cytosolic [Ca2+] stimulates myofilament force development
- Relaxation occurs when cytosolic [Ca2+] decreases
What senses the change due to depolarization?
Voltage-dependent Ca2+ channels
Voltage-dependent Ca2+ channels respond to the change by
allowing a small influx of Ca2+ ions to enter the cell
What does the influx of Ca2+ ion stimulate?
Release of lots of Ca2+ from the SR through RyRs
RyRs
Ryanodine Receptors
What is RyRs?
Intracellular Ca2+ gated Ca2+ release channels
What does RyRs do?
bind the plant alkaloid ryanodine with high specificity, blocking the channel
Increase in cytosolic [Ca2+] activates
[Ca2+] sensitive protein troponin C
What does the [Ca2+] sensitive protein troponin C stimulate?
contraction of the myofilaments
What does the extrusion of Ca2+ from the cytosol cause?
causes the muscle to relax
How does the extrusion occur?
a. reuptake of Ca2+ ions into the SR by the SR Ca2+ - ATPase pump
b. removal of Ca2+ ions from the cytosol by the Na+/Ca2+ - exchanger in the plasma membrane
What allows the reuptake of Ca2+ ions into the SR?
SR Ca2+ - ATPase pump
What allows the removal of Ca2+ ions from the cytosol
Na+/Ca2+ - exchanger
What is an another type of intracellular Ca2+ release channel?
IP3R
IP3R
Inositol 1,4,5-triphosphate receptor
What are the two distinct gene families of glucose transporter proteins that function in the plasma membrane?
a. GLUTs
b. Na+/glucose cotransporters
What are GLUTs?
uniporters which mediate facilitated transport of glucose down its concentration gradient
What does Na+/glucose cotransporter do?
couple the energy of the transmembrane Na+ gradient to the transport of glucose
GLUTs are part of what family?
Major facilitator superfamily (MFS)
What are MFS?
largest superfamily of proteins involved in the membrane transport
In whom are GLUTs found?
In all living organisms
What does GLUTS mediate?
the transport of solutes into or out of cells, depending on the solute concentrations
Why is GLUT-1 important?
to facilitate glucose into the brain
How does GLUT-1 facilitate glucose to brain?
By transporting glucose from the blood into endothelial cells, and then transporting glucose from the endothelial cell into the ECM, and then from the ECM into an astrocyte
What kind of transporter is GLUT-4
insulin-responsive transporter
What does GLUT-4 mediate?
mediates glucose uptake by muscle and adipose tissues
Where are GLUT-4 proteins located?
in the intracellular vesicles that fuse with the plasma membrane
What does the GLUT-4 proteins do?
Delivers the GLUT-4 transporters to the plasma membrane
What disease occurs if there is not enough GLUT-4 in the plasma membrane?
Type II diabetes
What two conformations to GLUT proteins alternate between?
a. glucose binding site faces the extracellular space
b. glucose binding site faces the cytosol
How does the binding of the glucose affect the orientation?
reorientation of the glucose-binding sites tot he opposite side of the membrane and in release of glucose
What do the symporters and antiporters move?
one solute against its transmembrane concentration gradient
What energy do the symporters and antiporters use?
uses the gradient energy of the second solute moving down its transmembrane concentration gradient
Symporters and antiporters are part of what family?
Major facilitator superfamily (MFS)
What is LacY?
bacterial lactose permease
a monomeric oligosaccahride/H+ symporter
What energy does LacY use to drive the accumulation of nutrients?
H+ gradient
LacY use what gradient to generate an H+ gradient?
Lactose gradient
How is the H+ gradient generated?
By a combination of ETS and by the F1F0 ATPase
Combination of ETS and F1F0 ATPase can couple?
ATP hydrolysis to the export of protons from the cytosol
Release of the lactose and protons into the cytosol induces a transition back to what conformation?
Outward-facing conformation
What are the 4 examples of a primary active transport protein that maintains the Na+ gradient?
a. voltage-dependent Na+ channels
b. epithelial Na+ channels
c. Na+/substrate transporters
d. Na+ dependent transporters involved in pH regulation
What are the 3 cotransporters of Na+/substrate transporters?
a. Na+/glucose symporter
b. Na+/iodide cotransporter
c. Na+/prooline cotransporter
How does Na+/glucose cotransporter work? (steps)
- Na+ binds
- conformational change
- sugar binds
- conformational change exposes Na+ and sugar to the intracellular side of the membrane
- released into the cytosol
- conformational, change and resetting to starting position
What is Na+/Ca2+ exchanger in excitable cells?
primary Ca2+ extrusion system to the ECM side of the plasma membrane
What does Na+/Ca2+ exchanger do?
transport 3 Na+ ions in exchange for 1 Ca2+ ion, generating a net electrogenic current of 1+ per cycle
What does Na+/K+/Cl- cotransporter mediate?
mediates electroneutral transport with a stoichiometry of 1:1:2
Under physiological conditions, where does Na+,K+,Cl- contransported to?
Into cells
Why is the Na+/K+/Cl- cotransporter important?
a. to maintain intracellular Cl- concentration
b. for the reabsorption of NaCl from the kidney to filtrate
What does Na+/Mg2+ exchanger do?
transports 2 Na+ ions in for each Mg2+ extruded, thus transport is electroneutral under physiologic conditions
Why is the Na+/Mg2+ exchanger important?
to get rid of excess Mg2+ that constantly permeates into the cytosol at a low rate
What energy does Na+/H+ exchanger and the Na+/HCO3- contransporter use?
energy of the transmembrane Na+ gradient to regulate pH
Lungs and kidneys help maintain the acid-base balance of the plasma by?
excreting CO2 out of the lungs and H+ into the urine
What secretes H+ into the lumenal filtrate (urine)?
apical membrane Na+/H+ exchanger (NHE)
The secretion of H+ into the lumenal filtrate is coupled to?
transport of an equal number of bicarbonate ions into the blood
What transports bicarbonate ions into the blood?
Na+/HCO3- cotransporter in the basolateral membrane of epithelial cells of the proximal tubule
What functions as the intracellular Ca2+ storage compartment?
ER
When does the resting Ca2+ concentrations reestablished?
after Ca2+ signaling has occurred
What are the main types of Ca2+ transport protein to extrude Ca2+ from the cytosol?
Ca2+ ATPase in the ER and in the plasma membrane
What in muscle cells gets most of the Ca2+ out?
SERCA (sarcoendoplasmic reticulum Ca2+ ATPase)
What sequences does the SERCA pump reaction cycle consist of?
sequence of phosphorylation and dephosphorylation events that power the uphill transport of 2 Ca2+ ions into the SR per hydrolyzed ATP in exchange for 2 H+ ions
PMCA (plasma membrane Ca2+ ATPase) pump function
transport 1 Ca2+ per ATP hydrolyzed