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

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2
Q

Structure of aquaporins

A

a. Homotetramers
b. each subunit forms a pore

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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

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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

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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

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6
Q

Vasopressin stimulates the expression of

A

Aquaporin-2

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7
Q

What does the stimulation of the expression of aquaporin-2 result in?

A

Increased urine concentration

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8
Q

Where is the aquaporin-2 expressed?

A

In the collecting ducts

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9
Q

What are the steps of action potential?

A
  1. opening of voltage-gated Na+ channels
  2. rapid flow of Na+ ions into the cell
  3. membrane depolarization
  4. depolarization stops within milliseconds, Na+ channels rapidly inactivate
  5. early repolarization begins, voltage-gated Ca2+ channels open
  6. transient outward K+ currents balance the Ca2+ channels
  7. more K+ ions rapidly exit the cell
  8. repolarization
  9. Na+/K+ - ATPase drives membrane potential toward repolarization to reestablish the resting negative membrane potential
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10
Q

What happens when depolarization stops?

A

Na+ channels rapidly inactivate

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11
Q

What happens when early repolarization begin?

A

voltage-gated Ca2+ channels open

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12
Q

What results after the K+ ions rapidly exit the cell?

A

repolarization

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13
Q

Ca2+ signaling regulates what?

A

muscle contraction and heart rhythm

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14
Q

Excitation-concentration coupling

A

Process in which membrane depolarization results in production of force by muscles (cardiac and skeletal)

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15
Q

What cell has much lower [Ca2+] compared to the extracellular or ER/SR concentrations?

A

Resting cells

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16
Q

Resting cells have much lower [Ca2+] compared to where?

A

the extracellular or ER/SR concentrations

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17
Q

When is the signal initiated at the plasma membrane?

A

when it is depolarized from an incoming action potential

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18
Q

What are the 4 steps of excitation-contraction coupling?

A
  1. Depolarization activates Ca2+ channels
  2. Ca2+ influx stimulates Ca2+ release from SR into cytosol
  3. Increased cytosolic [Ca2+] stimulates myofilament force development
  4. Relaxation occurs when cytosolic [Ca2+] decreases
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19
Q

What senses the change due to depolarization?

A

Voltage-dependent Ca2+ channels

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20
Q

Voltage-dependent Ca2+ channels respond to the change by

A

allowing a small influx of Ca2+ ions to enter the cell

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21
Q

What does the influx of Ca2+ ion stimulate?

A

Release of lots of Ca2+ from the SR through RyRs

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22
Q

RyRs

A

Ryanodine Receptors

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23
Q

What is RyRs?

A

Intracellular Ca2+ gated Ca2+ release channels

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24
Q

What does RyRs do?

A

bind the plant alkaloid ryanodine with high specificity, blocking the channel

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25
Q

Increase in cytosolic [Ca2+] activates

A

[Ca2+] sensitive protein troponin C

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26
Q

What does the [Ca2+] sensitive protein troponin C stimulate?

A

contraction of the myofilaments

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27
Q

What does the extrusion of Ca2+ from the cytosol cause?

A

causes the muscle to relax

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28
Q

How does the extrusion occur?

A

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

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29
Q

What allows the reuptake of Ca2+ ions into the SR?

A

SR Ca2+ - ATPase pump

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30
Q

What allows the removal of Ca2+ ions from the cytosol

A

Na+/Ca2+ - exchanger

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31
Q

What is an another type of intracellular Ca2+ release channel?

A

IP3R

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32
Q

IP3R

A

Inositol 1,4,5-triphosphate receptor

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33
Q

What are the two distinct gene families of glucose transporter proteins that function in the plasma membrane?

A

a. GLUTs
b. Na+/glucose cotransporters

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34
Q

What are GLUTs?

A

uniporters which mediate facilitated transport of glucose down its concentration gradient

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35
Q

What does Na+/glucose cotransporter do?

A

couple the energy of the transmembrane Na+ gradient to the transport of glucose

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36
Q

GLUTs are part of what family?

A

Major facilitator superfamily (MFS)

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37
Q

What are MFS?

A

largest superfamily of proteins involved in the membrane transport

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38
Q

In whom are GLUTs found?

A

In all living organisms

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39
Q

What does GLUTS mediate?

A

the transport of solutes into or out of cells, depending on the solute concentrations

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40
Q

Why is GLUT-1 important?

A

to facilitate glucose into the brain

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41
Q

How does GLUT-1 facilitate glucose to brain?

A

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

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42
Q

What kind of transporter is GLUT-4

A

insulin-responsive transporter

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43
Q

What does GLUT-4 mediate?

A

mediates glucose uptake by muscle and adipose tissues

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44
Q

Where are GLUT-4 proteins located?

A

in the intracellular vesicles that fuse with the plasma membrane

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45
Q

What does the GLUT-4 proteins do?

A

Delivers the GLUT-4 transporters to the plasma membrane

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46
Q

What disease occurs if there is not enough GLUT-4 in the plasma membrane?

A

Type II diabetes

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47
Q

What two conformations to GLUT proteins alternate between?

A

a. glucose binding site faces the extracellular space
b. glucose binding site faces the cytosol

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48
Q

How does the binding of the glucose affect the orientation?

A

reorientation of the glucose-binding sites tot he opposite side of the membrane and in release of glucose

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49
Q

What do the symporters and antiporters move?

A

one solute against its transmembrane concentration gradient

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50
Q

What energy do the symporters and antiporters use?

A

uses the gradient energy of the second solute moving down its transmembrane concentration gradient

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51
Q

Symporters and antiporters are part of what family?

A

Major facilitator superfamily (MFS)

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52
Q

What is LacY?

A

bacterial lactose permease
a monomeric oligosaccahride/H+ symporter

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53
Q

What energy does LacY use to drive the accumulation of nutrients?

A

H+ gradient

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54
Q

LacY use what gradient to generate an H+ gradient?

A

Lactose gradient

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55
Q

How is the H+ gradient generated?

A

By a combination of ETS and by the F1F0 ATPase

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56
Q

Combination of ETS and F1F0 ATPase can couple?

A

ATP hydrolysis to the export of protons from the cytosol

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57
Q

Release of the lactose and protons into the cytosol induces a transition back to what conformation?

A

Outward-facing conformation

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58
Q

What are the 4 examples of a primary active transport protein that maintains the Na+ gradient?

A

a. voltage-dependent Na+ channels
b. epithelial Na+ channels
c. Na+/substrate transporters
d. Na+ dependent transporters involved in pH regulation

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59
Q

What are the 3 cotransporters of Na+/substrate transporters?

A

a. Na+/glucose symporter
b. Na+/iodide cotransporter
c. Na+/prooline cotransporter

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60
Q

How does Na+/glucose cotransporter work? (steps)

A
  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
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61
Q

What is Na+/Ca2+ exchanger in excitable cells?

A

primary Ca2+ extrusion system to the ECM side of the plasma membrane

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62
Q

What does Na+/Ca2+ exchanger do?

A

transport 3 Na+ ions in exchange for 1 Ca2+ ion, generating a net electrogenic current of 1+ per cycle

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63
Q

What does Na+/K+/Cl- cotransporter mediate?

A

mediates electroneutral transport with a stoichiometry of 1:1:2

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64
Q

Under physiological conditions, where does Na+,K+,Cl- contransported to?

A

Into cells

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65
Q

Why is the Na+/K+/Cl- cotransporter important?

A

a. to maintain intracellular Cl- concentration
b. for the reabsorption of NaCl from the kidney to filtrate

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66
Q

What does Na+/Mg2+ exchanger do?

A

transports 2 Na+ ions in for each Mg2+ extruded, thus transport is electroneutral under physiologic conditions

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67
Q

Why is the Na+/Mg2+ exchanger important?

A

to get rid of excess Mg2+ that constantly permeates into the cytosol at a low rate

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68
Q

What energy does Na+/H+ exchanger and the Na+/HCO3- contransporter use?

A

energy of the transmembrane Na+ gradient to regulate pH

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69
Q

Lungs and kidneys help maintain the acid-base balance of the plasma by?

A

excreting CO2 out of the lungs and H+ into the urine

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70
Q

What secretes H+ into the lumenal filtrate (urine)?

A

apical membrane Na+/H+ exchanger (NHE)

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71
Q

The secretion of H+ into the lumenal filtrate is coupled to?

A

transport of an equal number of bicarbonate ions into the blood

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72
Q

What transports bicarbonate ions into the blood?

A

Na+/HCO3- cotransporter in the basolateral membrane of epithelial cells of the proximal tubule

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73
Q

What functions as the intracellular Ca2+ storage compartment?

A

ER

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74
Q

When does the resting Ca2+ concentrations reestablished?

A

after Ca2+ signaling has occurred

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75
Q

What are the main types of Ca2+ transport protein to extrude Ca2+ from the cytosol?

A

Ca2+ ATPase in the ER and in the plasma membrane

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76
Q

What in muscle cells gets most of the Ca2+ out?

A

SERCA (sarcoendoplasmic reticulum Ca2+ ATPase)

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77
Q

What sequences does the SERCA pump reaction cycle consist of?

A

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

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78
Q

PMCA (plasma membrane Ca2+ ATPase) pump function

A

transport 1 Ca2+ per ATP hydrolyzed

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79
Q

Similarity of SERCA and PMCA

A

a. P-type pumps
b. ATP dependent
c. use ATP to autophosphorylate a conserved aspartic acid residue

80
Q

5 Functions of membrane

A
  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
Q

What creates the electrochemical gradients?

A

the ion concentration difference inside and outside the cell

82
Q

Which ions have higher extracellular concentration (in the outside)?

A

Na+, Ca2+, and Cl-

83
Q

Which ions have higher intracellular concentration (inside)?

A

K+

84
Q

The charge inside the cell is _________ relative to the outside

A

negative

85
Q

How is the speed of the solute different in channel proteins and carriers?

A

Solute pass through channel proteins at high rate while they pass through carrier proteins much slower

86
Q

What three traits do channel proteins have?

A

a. high solute selectivity
b. a rapid rate of solute permeation
c. a gating mechanism

87
Q

What are 5 examples of channels?

A

a. ion channels
b. aquaporins
c. gap junctions
d. NPCs
e. ER protein translocators

88
Q

What does the selectivity filter allow?

A

Allow channel proteins to discriminate among different solutes

89
Q

How are channel proteins regulated?

A

By gating

90
Q

What are 4 types of gating?

A

a. ligand-gated
b. voltage-gated
c. stretch-activated
d. temperature-activated

91
Q

Electrochemical dictates the

A

direction of the movement

92
Q

What forms pores

A

channel proteins

93
Q

How do carrier proteins work?

A

solutes bind on one side of the membrane, undergo an allosteric change, and release them on the other side of the membrane

94
Q

Carrier proteins transduce energy from

A

a. electrochemical gradients
b. ATP
c. other energy sources

95
Q

What are the two main types of a carrier protein?

A

transporters and pump

96
Q

Transporters

A

couple energy from electrochemical membrane gradients to facilitate movement of substrate across the membrane

97
Q

What are the three types of transporters?

A

a. uniporters
b. symporters (cotransporters)
c. antiporters (exchangers)

98
Q

Pumps

A

uses energy directly to drive energetically less favorable substrate accumulation or efflux

99
Q

What does primary active transport (pumps) do?

A

drive transport of solutes against their electrochemical gradients

100
Q

What energy does primary active transport use?

A

ATP

101
Q

Primary active transport works to

A

maintain gradient of solutes across membranes

102
Q

What 2 examples of primary active transport?

A

a. Ca2+ ATPase
b. Na+/K+ ATPase

103
Q

What does secondary active transport (transporters) do?

A

drives trans-membrane solute transport

104
Q

What energy does secondary active transport use?

A

use the free energy stored in the electrochemical gradients
do not use ATP directly

105
Q

Ions in solution surrounded by

A

water molecules are attracted by their dipolar partial negative and partial positive charges

106
Q

What is formed around each ion

A

hydration shell

107
Q

Formation of hydration shell is energetically _________.

A

favorable because it requires lots of energy to move into a lipid bilayer

108
Q

Size of the hydration shell depends upon

A

the charge density and size of the ion

109
Q

Ion channels enable the ___________ ______________ of ions as they travel through

A

partial dehydration

110
Q

As ions goes through the ion channel, it forms a weak bond with what and why?

A

amino acid residues, which help make the transport process energetically favorable and selective

111
Q

When does a membrane potential exist?

A

when there is an electrochemical gradient

112
Q

A membrane potential requires

A

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
Q

What three ions are major contributors to the membrane potential?

A

K+, Na+, and Cl-

114
Q

What two ions contribute little to the resting membrane potential?

A

Ca2+ and Mg2+

115
Q

K+ leak channels allow

A

K+ ions out of the cell, down their electrochemical gradient

116
Q

K+ leak channels help

A

to make the inside of the cell more negative

117
Q

Na+/K+ ATPase function

A

pumps 2 K+ ions into the cell for every 3 Na+ it pumps out

118
Q

Na+/K+ ATPase helps to

A

a. make inside more negative
b. increase the K+ gradient so the leak channels can keep working

119
Q

How does depolarization occurs?

A

when Na+ or Ca2+ channels open, the ions flow into the cell

120
Q

How does repolarization occur?

A

when K+ channels open, K+ moves out of the cell

121
Q

Depolarization makes the membrane potential more

A

positive

122
Q

Repolarization makes the membrane potential more

A

negative

123
Q

K+ channels form a

A

narrow water-filled pore

124
Q

Structure of K+ channels

A

a. tetramers
b. each identical subunit contributes to a central pore

125
Q

What are the two main parts of the K+ channel?

A

central cavity and selectivity filter

126
Q

Central cavity help

A

stabilize K+ ions before they go through

127
Q

Selectivity filter has to ________ the ions in order for them to pass through

A

dehydrate

128
Q

How is the dehydration of ion enabled by the selectivity filter?

A

enabled due to the partial negative charge of the oxygen atoms in the selectivity filter which acts as surrogate water molecules

129
Q

What are three K+ channel subfamilies?

A
  1. gates sensitive to metabolic state of the cell
  2. gates sensitive to ligand binding
  3. gates sensitive to voltage
130
Q

2 examples of K+ channels

A

a. Ca2+ activated K+ channel
b. voltage-gated K+ channel

131
Q

Voltage-gated channels sense

A

changes of the membrane electric field via several positively charged amino acid residues in their voltage-sensing module of their transmembrane domains

132
Q

Voltage-dependent Na+ channels require what gradient

A

electrochemical Na+ gradient

133
Q

The electrochemical Na+ gradient is generated by

A

Na+/K+ ATPase

134
Q

IMPs formed with

A

single pore-forming subunit

135
Q

IMPs transport

A

Na+ ions down their electrochemical gradient

136
Q

After voltage-dependent activation what occurs very quickly?

A

voltage-dependent inactivation of Na+ channels

137
Q

The selectivity filter of Na+ channels bind to

A

tetrodotoxin from puffer fish

138
Q

Binding of tetrodotoxin to the selectivity filter causes

A

paralysis by inactivating voltage-gated Na+ channels involved in the initiation and propagation of action potentials in nerve cells

139
Q

Na+ channels are targets for

A

local anesthetics and drugs used to treat cardiac arrhythmias

140
Q

Drugs that used to treat cardiac arrhythmias inhibit

A

membrane depolarization

141
Q

ENaC

A

Epithelial Na+ channels

142
Q

ENaCs are regulated by

A

hormones

143
Q

ENaCs first found in

A

epithelial cells

144
Q

ENaCs mediate

A

bulk flow of Na+ ions, influence water transport across cell layers

145
Q

ENaCs function depends on

A

Na+ gradient established by the Na+/K+ ATPase

146
Q

Where are ENaCs located?

A

in the apical membrane of epithelial cells in the distal tubule and collecting ducts of each kidney nephron

147
Q

ENaCs allow

A

Na+ ions from the filtrate to enter the cells down their gradient

148
Q

Na+/K+ ATPase help by

A

removing Na+ from the epithelial cell and transporting it back into the blood capillary

149
Q

Reabsorption of Na+ is regulated by

A

aldosterone from the adrenal glands and vasopressin from the pituitary gland

150
Q

Aldosterone bind to receptors on

A

kidney cells

151
Q

Mutation in ENaC, increasing Na+ reabsorption results in

A

high blood plasma volume, hypertension, and low plasma K+

152
Q

A diuretic drug that blocks the Na+ reabsorption by ENaC

A

amiloride

153
Q

Amiloride blocks Na+ reabsorption by ENaC in?

A

lumenal membrane of the kidney distal tubule and collecting duct

154
Q

Amiloride results in

A

decreased Na+ reabsorption, lower Na+ concentration in blood, and lower or normalized blood pressure

155
Q

Where are Ca2+ concentrations high?

A

In the extracellular fluid and in ER and SR

156
Q

Ca2+ channels are gated by

A

extracellular ligands, voltage changes, or Ca2+ itself

157
Q

Influx of Ca2+ increases the intracellular [Ca2+] to a level that triggers responses such as

A

a. muscle contraction
b. hormone or neurotransmitter release
c. activation of Ca2+ dependent signaling cascades
d. gene transcription

158
Q

In in vitro assays, Cl- channels function as

A

nonselective anion channels

159
Q

What are the three different gene families?

A
  1. CLC gene family
  2. Cystic fibrosis transmembrane conductance regulator
  3. Ligand-gated (GABA receptor and glycine receptor family)
160
Q

Cl- is the most abundant anion

A

in vivo assay

161
Q

Cystic fibrosis transmembrane conductance regulator is part of what family

A

ABC transporter family

162
Q

ABC

A

ATP binding cassette where every member of family needs to bind to ATP

163
Q

What are the 2 major components of the electrochemical gradient across the eukaryotic plasma membrane?

A

Na+ and K+ gradients

164
Q

What does the negative resting membrane potential regulate?

A

osmotic pressure

165
Q

What does the negative resting membrane potential allows

A

secondary Na+ dependent transport of molecules

166
Q

Electrochemical gradient is generated and maintained by

A

Na+/K+ ATPase

167
Q

Na+/K+ ATPase belongs to the family of

A

P-type ATPases

168
Q

Belonging to the family of P-type ATPase means

A

it autophosphorylates an aspartic acid residue as an intermediate during ion transport

169
Q

Terminal phosphate is transferred from

A

ATP to the active site in the enzyme

170
Q

For each ATP hydrolyzed, how many Na+ are moved out and K+ are moved in/from where?

A

3 Na+ out and 2K+ from ECF into the cytosol

171
Q

Through Na+/K+ ATPase, what is created across the plasma membrane?

A

an electrical potential difference and an osmotic ion gradient

172
Q

Sodium potassium is _________ but not under _________ conditions

A

reversible; physiological

173
Q

What targets the sodium potassium pump?

A

various toxins and drugs
plant steroids called cardiac glycosides

174
Q

Cardiac glycosides function

A

inhibit ion transport by sodium potassium pump

175
Q

Where does digitalis come from?

A

foxglove plants

176
Q

Digitalis is used to

A

treat heart failure because a small amount will increase cytoplasmic [Na+] which results in higher cytoplasmic [Ca2+] which increase contractility of the heart

177
Q

Target of digitalis

A

Sodium potassium pump

178
Q

F1F0 ATP synthase couples

A

H+ movement to ATP synthesis or hydrolysis

179
Q

F1F0 ATP synthase is a

A

molecular motor

180
Q

F1F0 ATP synthase couples the energy of the electrochemical proton gradient across

A

the plasma membrane of prokaryotic cells or the mitochondrial inner membrane of eukaryotic cells to ATP synthesis

181
Q

The transmembrane domain of F1F0 ATP synthase is the

A

F0 region

182
Q

F0 region is involved in

A

translocation of protons down their electrochemical gradient

183
Q

F0 region is the

A

transmembrane domain

184
Q

The cytoplasmic or mitochondrial matrix globular domain is the

A

F1 region

185
Q

F1 region contains the

A

catalytic sites responsible for ATP synthesis

186
Q

F1 region is the

A

cytoplasmic or mitochondrial matrix globular domain

187
Q

In F1F0 ATP synthase, per ATP synthesized, how many protons are transported?

A

4

188
Q

In F1F0 ATP synthase, ATP synthesis occurs at a rate of

A

~100/sec

189
Q

F1F0 ATP synthase can work in

A

reverse

190
Q

In F1F0 ATP synthase, some bacterial cells can use

A

ATP hydrolysis to generate a H+ gradient which other membrane proteins can use to move solutes

191
Q

H+ ATPase transport

A

protons out of the cytosol

192
Q

V-ATPase

A

Vacuolar-type proton pumps

193
Q

V-ATPases are

A

H+ ATPases

194
Q

V-ATPases essential for

A

maintaining the pH of organelles such as lysosomes, endosomes, which need a more acidic environment than the cytosol

195
Q
A
196
Q

2 functional domains of H+ ATPases

A

V1 (cytosolic) and V0 domain

197
Q

V1 function

A

binds and hydrolyses ATP, providing the energy for proton translocation across the membrane bound V0 domain