Chapter 6 Flashcards
1
Q
Aquaporins are involved in
A
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
2
Q
Structure of aquaporins
A
a. Homotetramers
b. each subunit forms a pore
3
Q
What are the three features that confer the water-specificity of aquaporin?
A
a. size restriction via a constriction region
b. electrostatic repulsion
c. water dipole orientation
4
Q
In kidneys, what does the aquaporin-1 type protein channels do?
A
Help concentrate 180 liters of blood filtrate per day into a urine volume of 1.5 liters per day by reabsorbing
5
Q
Where does the aquaporin-1 have a constitutive high water permeability?
A
In the epithelial cells of the proximal convoluted tubules and descending thin limbs of the loop of Henle
6
Q
Vasopressin stimulates the expression of
A
Aquaporin-2
7
Q
What does the stimulation of the expression of aquaporin-2 result in?
A
Increased urine concentration
8
Q
Where is the aquaporin-2 expressed?
A
In the collecting ducts
9
Q
What are the steps of action potential?
A
- 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
10
Q
What happens when depolarization stops?
A
Na+ channels rapidly inactivate
11
Q
What happens when early repolarization begin?
A
voltage-gated Ca2+ channels open
12
Q
What results after the K+ ions rapidly exit the cell?
A
repolarization
13
Q
Ca2+ signaling regulates what?
A
muscle contraction and heart rhythm
14
Q
Excitation-concentration coupling
A
Process in which membrane depolarization results in production of force by muscles (cardiac and skeletal)
15
Q
What cell has much lower [Ca2+] compared to the extracellular or ER/SR concentrations?
A
Resting cells
16
Q
Resting cells have much lower [Ca2+] compared to where?
A
the extracellular or ER/SR concentrations
17
Q
When is the signal initiated at the plasma membrane?
A
when it is depolarized from an incoming action potential
18
Q
What are the 4 steps of excitation-contraction coupling?
A
- 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
19
Q
What senses the change due to depolarization?
A
Voltage-dependent Ca2+ channels
20
Q
Voltage-dependent Ca2+ channels respond to the change by
A
allowing a small influx of Ca2+ ions to enter the cell
21
Q
What does the influx of Ca2+ ion stimulate?
A
Release of lots of Ca2+ from the SR through RyRs
22
Q
RyRs
A
Ryanodine Receptors
23
Q
What is RyRs?
A
Intracellular Ca2+ gated Ca2+ release channels
24
Q
What does RyRs do?
A
bind the plant alkaloid ryanodine with high specificity, blocking the channel
25
Increase in cytosolic [Ca2+] activates
[Ca2+] sensitive protein troponin C
26
What does the [Ca2+] sensitive protein troponin C stimulate?
contraction of the myofilaments
27
What does the extrusion of Ca2+ from the cytosol cause?
causes the muscle to relax
28
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
29
What allows the reuptake of Ca2+ ions into the SR?
SR Ca2+ - ATPase pump
30
What allows the removal of Ca2+ ions from the cytosol
Na+/Ca2+ - exchanger
31
What is an another type of intracellular Ca2+ release channel?
IP3R
32
IP3R
Inositol 1,4,5-triphosphate receptor
33
What are the two distinct gene families of glucose transporter proteins that function in the plasma membrane?
a. GLUTs
b. Na+/glucose cotransporters
34
What are GLUTs?
uniporters which mediate facilitated transport of glucose down its concentration gradient
35
What does Na+/glucose cotransporter do?
couple the energy of the transmembrane Na+ gradient to the transport of glucose
36
GLUTs are part of what family?
Major facilitator superfamily (MFS)
37
What are MFS?
largest superfamily of proteins involved in the membrane transport
38
In whom are GLUTs found?
In all living organisms
39
What does GLUTS mediate?
the transport of solutes into or out of cells, depending on the solute concentrations
40
Why is GLUT-1 important?
to facilitate glucose into the brain
41
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
42
What kind of transporter is GLUT-4
insulin-responsive transporter
43
What does GLUT-4 mediate?
mediates glucose uptake by muscle and adipose tissues
44
Where are GLUT-4 proteins located?
in the intracellular vesicles that fuse with the plasma membrane
45
What does the GLUT-4 proteins do?
Delivers the GLUT-4 transporters to the plasma membrane
46
What disease occurs if there is not enough GLUT-4 in the plasma membrane?
Type II diabetes
47
What two conformations to GLUT proteins alternate between?
a. glucose binding site faces the extracellular space
b. glucose binding site faces the cytosol
48
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
49
What do the symporters and antiporters move?
one solute against its transmembrane concentration gradient
50
What energy do the symporters and antiporters use?
uses the gradient energy of the second solute moving down its transmembrane concentration gradient
51
Symporters and antiporters are part of what family?
Major facilitator superfamily (MFS)
52
What is LacY?
bacterial lactose permease
a monomeric oligosaccahride/H+ symporter
53
What energy does LacY use to drive the accumulation of nutrients?
H+ gradient
54
LacY use what gradient to generate an H+ gradient?
Lactose gradient
55
How is the H+ gradient generated?
By a combination of ETS and by the F1F0 ATPase
56
Combination of ETS and F1F0 ATPase can couple?
ATP hydrolysis to the export of protons from the cytosol
57
Release of the lactose and protons into the cytosol induces a transition back to what conformation?
Outward-facing conformation
58
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
59
What are the 3 cotransporters of Na+/substrate transporters?
a. Na+/glucose symporter
b. Na+/iodide cotransporter
c. Na+/prooline cotransporter
60
How does Na+/glucose cotransporter work? (steps)
1. Na+ binds
2. conformational change
3. sugar binds
4. conformational change exposes Na+ and sugar to the intracellular side of the membrane
5. released into the cytosol
6. conformational, change and resetting to starting position
61
What is Na+/Ca2+ exchanger in excitable cells?
primary Ca2+ extrusion system to the ECM side of the plasma membrane
62
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
63
What does Na+/K+/Cl- cotransporter mediate?
mediates electroneutral transport with a stoichiometry of 1:1:2
64
Under physiological conditions, where does Na+,K+,Cl- contransported to?
Into cells
65
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
66
What does Na+/Mg2+ exchanger do?
transports 2 Na+ ions in for each Mg2+ extruded, thus transport is electroneutral under physiologic conditions
67
Why is the Na+/Mg2+ exchanger important?
to get rid of excess Mg2+ that constantly permeates into the cytosol at a low rate
68
What energy does Na+/H+ exchanger and the Na+/HCO3- contransporter use?
energy of the transmembrane Na+ gradient to regulate pH
69
Lungs and kidneys help maintain the acid-base balance of the plasma by?
excreting CO2 out of the lungs and H+ into the urine
70
What secretes H+ into the lumenal filtrate (urine)?
apical membrane Na+/H+ exchanger (NHE)
71
The secretion of H+ into the lumenal filtrate is coupled to?
transport of an equal number of bicarbonate ions into the blood
72
What transports bicarbonate ions into the blood?
Na+/HCO3- cotransporter in the basolateral membrane of epithelial cells of the proximal tubule
73
What functions as the intracellular Ca2+ storage compartment?
ER
74
When does the resting Ca2+ concentrations reestablished?
after Ca2+ signaling has occurred
75
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
76
What in muscle cells gets most of the Ca2+ out?
SERCA (sarcoendoplasmic reticulum Ca2+ ATPase)
77
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
78
PMCA (plasma membrane Ca2+ ATPase) pump function
transport 1 Ca2+ per ATP hydrolyzed
79
Similarity of SERCA and PMCA
a. P-type pumps
b. ATP dependent
c. use ATP to autophosphorylate a conserved aspartic acid residue
80
5 Functions of membrane
1. maintain homeostasis
2. control solute concentrations across membrane
3. adapt to altered metabolic situation
4. process info
5. transport nutrient in and waste products out
81
What creates the electrochemical gradients?
the ion concentration difference inside and outside the cell
82
Which ions have higher extracellular concentration (in the outside)?
Na+, Ca2+, and Cl-
83
Which ions have higher intracellular concentration (inside)?
K+
84
The charge inside the cell is _________ relative to the outside
negative
85
How is the speed of the solute different in channel proteins and carriers?
Solute pass through channel proteins at high rate while they pass through carrier proteins much slower
86
What three traits do channel proteins have?
a. high solute selectivity
b. a rapid rate of solute permeation
c. a gating mechanism
87
What are 5 examples of channels?
a. ion channels
b. aquaporins
c. gap junctions
d. NPCs
e. ER protein translocators
88
What does the selectivity filter allow?
Allow channel proteins to discriminate among different solutes
89
How are channel proteins regulated?
By gating
90
What are 4 types of gating?
a. ligand-gated
b. voltage-gated
c. stretch-activated
d. temperature-activated
91
Electrochemical dictates the
direction of the movement
92
What forms pores
channel proteins
93
How do carrier proteins work?
solutes bind on one side of the membrane, undergo an allosteric change, and release them on the other side of the membrane
94
Carrier proteins transduce energy from
a. electrochemical gradients
b. ATP
c. other energy sources
95
What are the two main types of a carrier protein?
transporters and pump
96
Transporters
couple energy from electrochemical membrane gradients to facilitate movement of substrate across the membrane
97
What are the three types of transporters?
a. uniporters
b. symporters (cotransporters)
c. antiporters (exchangers)
98
Pumps
uses energy directly to drive energetically less favorable substrate accumulation or efflux
99
What does primary active transport (pumps) do?
drive transport of solutes against their electrochemical gradients
100
What energy does primary active transport use?
ATP
101
Primary active transport works to
maintain gradient of solutes across membranes
102
What 2 examples of primary active transport?
a. Ca2+ ATPase
b. Na+/K+ ATPase
103
What does secondary active transport (transporters) do?
drives trans-membrane solute transport
104
What energy does secondary active transport use?
use the free energy stored in the electrochemical gradients
do not use ATP directly
105
Ions in solution surrounded by
water molecules are attracted by their dipolar partial negative and partial positive charges
106
What is formed around each ion
hydration shell
107
Formation of hydration shell is energetically _________.
favorable because it requires lots of energy to move into a lipid bilayer
108
Size of the hydration shell depends upon
the charge density and size of the ion
109
Ion channels enable the ___________ ______________ of ions as they travel through
partial dehydration
110
As ions goes through the ion channel, it forms a weak bond with what and why?
amino acid residues, which help make the transport process energetically favorable and selective
111
When does a membrane potential exist?
when there is an electrochemical gradient
112
A membrane potential requires
a. the ion concentration differences across the membrane resulting in a charge separation
b. a membrane which is selectively permeable for at least one of the ionic species
113
What three ions are major contributors to the membrane potential?
K+, Na+, and Cl-
114
What two ions contribute little to the resting membrane potential?
Ca2+ and Mg2+
115
K+ leak channels allow
K+ ions out of the cell, down their electrochemical gradient
116
K+ leak channels help
to make the inside of the cell more negative
117
Na+/K+ ATPase function
pumps 2 K+ ions into the cell for every 3 Na+ it pumps out
118
Na+/K+ ATPase helps to
a. make inside more negative
b. increase the K+ gradient so the leak channels can keep working
119
How does depolarization occurs?
when Na+ or Ca2+ channels open, the ions flow into the cell
120
How does repolarization occur?
when K+ channels open, K+ moves out of the cell
121
Depolarization makes the membrane potential more
positive
122
Repolarization makes the membrane potential more
negative
123
K+ channels form a
narrow water-filled pore
124
Structure of K+ channels
a. tetramers
b. each identical subunit contributes to a central pore
125
What are the two main parts of the K+ channel?
central cavity and selectivity filter
126
Central cavity help
stabilize K+ ions before they go through
127
Selectivity filter has to ________ the ions in order for them to pass through
dehydrate
128
How is the dehydration of ion enabled by the selectivity filter?
enabled due to the partial negative charge of the oxygen atoms in the selectivity filter which acts as surrogate water molecules
129
What are three K+ channel subfamilies?
1. gates sensitive to metabolic state of the cell
2. gates sensitive to ligand binding
3. gates sensitive to voltage
130
2 examples of K+ channels
a. Ca2+ activated K+ channel
b. voltage-gated K+ channel
131
Voltage-gated channels sense
changes of the membrane electric field via several positively charged amino acid residues in their voltage-sensing module of their transmembrane domains
132
Voltage-dependent Na+ channels require what gradient
electrochemical Na+ gradient
133
The electrochemical Na+ gradient is generated by
Na+/K+ ATPase
134
IMPs formed with
single pore-forming subunit
135
IMPs transport
Na+ ions down their electrochemical gradient
136
After voltage-dependent activation what occurs very quickly?
voltage-dependent inactivation of Na+ channels
137
The selectivity filter of Na+ channels bind to
tetrodotoxin from puffer fish
138
Binding of tetrodotoxin to the selectivity filter causes
paralysis by inactivating voltage-gated Na+ channels involved in the initiation and propagation of action potentials in nerve cells
139
Na+ channels are targets for
local anesthetics and drugs used to treat cardiac arrhythmias
140
Drugs that used to treat cardiac arrhythmias inhibit
membrane depolarization
141
ENaC
Epithelial Na+ channels
142
ENaCs are regulated by
hormones
143
ENaCs first found in
epithelial cells
144
ENaCs mediate
bulk flow of Na+ ions, influence water transport across cell layers
145
ENaCs function depends on
Na+ gradient established by the Na+/K+ ATPase
146
Where are ENaCs located?
in the apical membrane of epithelial cells in the distal tubule and collecting ducts of each kidney nephron
147
ENaCs allow
Na+ ions from the filtrate to enter the cells down their gradient
148
Na+/K+ ATPase help by
removing Na+ from the epithelial cell and transporting it back into the blood capillary
149
Reabsorption of Na+ is regulated by
aldosterone from the adrenal glands and vasopressin from the pituitary gland
150
Aldosterone bind to receptors on
kidney cells
151
Mutation in ENaC, increasing Na+ reabsorption results in
high blood plasma volume, hypertension, and low plasma K+
152
A diuretic drug that blocks the Na+ reabsorption by ENaC
amiloride
153
Amiloride blocks Na+ reabsorption by ENaC in?
lumenal membrane of the kidney distal tubule and collecting duct
154
Amiloride results in
decreased Na+ reabsorption, lower Na+ concentration in blood, and lower or normalized blood pressure
155
Where are Ca2+ concentrations high?
In the extracellular fluid and in ER and SR
156
Ca2+ channels are gated by
extracellular ligands, voltage changes, or Ca2+ itself
157
Influx of Ca2+ increases the intracellular [Ca2+] to a level that triggers responses such as
a. muscle contraction
b. hormone or neurotransmitter release
c. activation of Ca2+ dependent signaling cascades
d. gene transcription
158
In in vitro assays, Cl- channels function as
nonselective anion channels
159
What are the three different gene families?
1. CLC gene family
2. Cystic fibrosis transmembrane conductance regulator
3. Ligand-gated (GABA receptor and glycine receptor family)
160
Cl- is the most abundant anion
in vivo assay
161
Cystic fibrosis transmembrane conductance regulator is part of what family
ABC transporter family
162
ABC
ATP binding cassette where every member of family needs to bind to ATP
163
What are the 2 major components of the electrochemical gradient across the eukaryotic plasma membrane?
Na+ and K+ gradients
164
What does the negative resting membrane potential regulate?
osmotic pressure
165
What does the negative resting membrane potential allows
secondary Na+ dependent transport of molecules
166
Electrochemical gradient is generated and maintained by
Na+/K+ ATPase
167
Na+/K+ ATPase belongs to the family of
P-type ATPases
168
Belonging to the family of P-type ATPase means
it autophosphorylates an aspartic acid residue as an intermediate during ion transport
169
Terminal phosphate is transferred from
ATP to the active site in the enzyme
170
For each ATP hydrolyzed, how many Na+ are moved out and K+ are moved in/from where?
3 Na+ out and 2K+ from ECF into the cytosol
171
Through Na+/K+ ATPase, what is created across the plasma membrane?
an electrical potential difference and an osmotic ion gradient
172
Sodium potassium is _________ but not under _________ conditions
reversible; physiological
173
What targets the sodium potassium pump?
various toxins and drugs
plant steroids called cardiac glycosides
174
Cardiac glycosides function
inhibit ion transport by sodium potassium pump
175
Where does digitalis come from?
foxglove plants
176
Digitalis is used to
treat heart failure because a small amount will increase cytoplasmic [Na+] which results in higher cytoplasmic [Ca2+] which increase contractility of the heart
177
Target of digitalis
Sodium potassium pump
178
F1F0 ATP synthase couples
H+ movement to ATP synthesis or hydrolysis
179
F1F0 ATP synthase is a
molecular motor
180
F1F0 ATP synthase couples the energy of the electrochemical proton gradient across
the plasma membrane of prokaryotic cells or the mitochondrial inner membrane of eukaryotic cells to ATP synthesis
181
The transmembrane domain of F1F0 ATP synthase is the
F0 region
182
F0 region is involved in
translocation of protons down their electrochemical gradient
183
F0 region is the
transmembrane domain
184
The cytoplasmic or mitochondrial matrix globular domain is the
F1 region
185
F1 region contains the
catalytic sites responsible for ATP synthesis
186
F1 region is the
cytoplasmic or mitochondrial matrix globular domain
187
In F1F0 ATP synthase, per ATP synthesized, how many protons are transported?
4
188
In F1F0 ATP synthase, ATP synthesis occurs at a rate of
~100/sec
189
F1F0 ATP synthase can work in
reverse
190
In F1F0 ATP synthase, some bacterial cells can use
ATP hydrolysis to generate a H+ gradient which other membrane proteins can use to move solutes
191
H+ ATPase transport
protons out of the cytosol
192
V-ATPase
Vacuolar-type proton pumps
193
V-ATPases are
H+ ATPases
194
V-ATPases essential for
maintaining the pH of organelles such as lysosomes, endosomes, which need a more acidic environment than the cytosol
195
196
2 functional domains of H+ ATPases
V1 (cytosolic) and V0 domain
197
V1 function
binds and hydrolyses ATP, providing the energy for proton translocation across the membrane bound V0 domain
