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physiology and pharmacology > cell membranes > Flashcards

cell membranes Flashcards

1
Q

what does the cell membrane divide?

A

the intracellular and extracellular fluid compartments

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2
Q

what is the composition of a cell membrane? percentages>

A

lipids 42% weight
proteins 55% weight
carbohydrates 3% weight

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3
Q

in the plasma and interstitial fluid what are the concentrations of sodium and potassium like?

A

there’s lots of sodium and a low potassium concentration

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4
Q

what are the intracellular fluid concentrations of sodium and potassium like?

A

there’s lots of potassium and little sodium

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5
Q

what are chloride concentrations like in the plasma, intersticial fluid and the intracellular fluid? is this true for all cells?

A

in the plasma and ISF they are at mM concs where as in the ICF it is in nM. for most cells it’s true however for those cells that secrete Chloride ions it isn’t true.

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6
Q

question about bicarbonate here

A

put answer here

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7
Q

why are phosphate levels high intracellularly?

A

because of ATP synthesis

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8
Q

what are protein levels like in the plasma ISF and ICF

A

plasma levels are higher than the ISF levels, however there’s a lot more protein intracellularly.

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9
Q

how do lipid soluble molecules pass across the membrane?

A

through diffusion

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10
Q

how do small molecules/ ions pass across the membrane?

A

transport proteins

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11
Q

how to large molecules pass across the membrane?

A

through endocytosis or exocytosis

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12
Q

what are the three types of transporters?

A

carriers, pumps and channels

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13
Q

what are carriers? (2)

A

they are facillitates transport proteins, and secondary active transport proteins

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14
Q

what does secondary active transport protein mean?

A

it means it’s indirectly dependant on ATP, as an ATPase is also needed in order for this carrier to work properly

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15
Q

how do pumps work?

A

they are primary active transport proteins meaning they need to hydrolyse ATP as they are directly dependant on it.

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16
Q

what’s an electrochemical gradient?

A

the overall driving force which depends on potential and concentration

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17
Q

what kind of turnover does active transport have?

A

a low one,

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18
Q

what are 3 properties of the na/k ATPase

A
  1. ubiquitous
  2. tetramer
  3. 3Na: 2 K electrogenic
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19
Q

why is na/k ATPase a tetramer?

A

because it is made up of 4 subunits

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20
Q

what subunits is the na/k ATPase made up of?

A

2 alpha and 2 beta subunits

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21
Q

what does the na/k ATPase do? what would happen if it was stopped?

A

maintains the low intracellular sodium concentrations, if this was stopped it would stop the cell functioning

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22
Q

how does passive transport work? what does it depend on?

A

it follows the elctrochemical gradient which means it’s dependant on the concentration and the potential.

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23
Q

what kind of diffusion do carriers use?

A

facilliated diffusion

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24
Q

what are the three basic steps of a carrier in action

A
  1. binding
  2. conformational change
  3. release
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25
Q

what kind of turnover do carriers have? how selective are they?

A

a high turnover, 10 to the power 2 - 10 to the power 3 of ions per second.. they are highly selective

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26
Q

what does it mean when saturation is said in reference to carriers?

A

that if the ion concentration is continuously increased it will reach a maximum transport rate.

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27
Q

what’s a uniporter
what’s a symporter
what’s a antiporter

A
  1. one ion or solute at a time
  2. a co transporter in the same direction
  3. and exchanger where as one comes in one goes out
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28
Q

why is there a current in an open channel but not a closed one?

A

because open channels are conductive which allows an ion flow where as closed channels aren’t

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29
Q

why is a current generated through channels?

A

because ions flow through and these ions are charged, this creates a current.

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30
Q

what kind of turnover do channels have? why is this?

A

a high turnover, 10 to the power 6 to ten to the power 8 ions per second. this is because there are multiple ions going through the pore at one time in a pore like fashion.

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31
Q

what kind of channels are there?

A

na, cl , k , ca and non selective channels

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32
Q

what are non selective channels?

A

they allow different ions to pass through

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33
Q

what is the patch clamp technique?

A

it allows the current to be measured through either a single pore or numerous pores.

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34
Q

what is the cell attached configuration of the patch clamp technique? why does this work?

A

when the tip of the electrode is sealed to the cell surface as the lipid seals to the glass. the cell membrane isn’t broken as the tip is one micron making it relatively large to the cell and not sharp.

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35
Q

what units are ion channels currents measured in?

A

in PA which is 10 to the -12(VERY SMALL)

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36
Q

what is the whole cell configuration of the patch clamp technique?

A

when the cell attached configuration is continued with the electrode sucking more causing the cell membrane to rupture so the current of the whole cell can be taken

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37
Q

what did the development of patch clamp allow

A

ion channels to be identified, what kind they are, what regulated by, what physiological function

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38
Q

how can the current of a cell be changed? (3)

A

by changing the number of channels
by changing the open probability
or by changing the driving force

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39
Q

how can the number of channels be changed?

A

through membrane shuttling

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40
Q

how can the open probability be altered? (3)

A

through phosphorylation, calcium, G-proteins etc

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41
Q

how can the Vm be changed?

A

by activation or inhibition of other channels

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42
Q

how can ion channels be classified?

A

based on their molecular sequence, amino acid sequence and structure

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43
Q

what is the membrane potential (Vm) set by?

A

by potassium pumps

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44
Q

how is Vm measured?

A

a glass electrode that has a salt solution inside goes through the lipid bilayer, this measures the intracellular potential in comparison to the extracellular

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45
Q

what kind of elecrode is used when measuring Vm

A

a intracellular electrode

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46
Q

what’s the difference between the intracellular electrode and the electrode used in the patch clamp

A

the electrode in Vm measurement is much smaller than that used in patch clamp

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47
Q

what is the resting membrane potential? what is this?

A

it is around -70Vm, it’s the unequal distribution and selective movement of few ions.

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48
Q

how are Na and K concentrations maintained at resting potential

A

maintained by the na/k ATPase

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49
Q

what does it mean when something is electrogenic?

A

there is a net movement of charge which in turn changes the potential

50
Q

why is the na/k ATPase electrogenic?

A

because 3 positively charged na are leaving and 2 positively charged k are entering, leaving a negative potential

51
Q

what is the nernst potential?

A

when there’s no net movement of ions, resulting in no current.

52
Q

what happens when potassium channels open? does this just continue to happen whilst the channels are open?

A

potassium moves out of the cell due to the high intercellular concentration, this doesn’t just continue to happen as when the potassium leaved the potential becomes more negative, this attracting the positively charged potassium and pulling it back.

53
Q

what happens if concentration gradient is larger than potential drive and visa versa

A

if conc gradient is larger then potassium leaves the cell. if potential drive is larger then potassium moves back into the cell.

54
Q

why is the Vm for potassium never actually 90.1 as predicted by the nernst equation?

A

because there’s a small sodium leakage out of potassium channels

55
Q

what happens when sodium channels open is this the case for however long the channels are open for?

A

when the channels open sodium moves down the concentration gradient into the cell, however as sodium is entering the Vm is becoming positive, this positive charge in turn does start to repel the positively charged sodium.

56
Q

how is it known that potassium channels underpin the permeability of the cell?

A

because the Vm is closer to the Ek than the ENa

57
Q

what happens to the Vm during depolarisation?

A

the Vm moves toward the Na nernst potential as sodium channels have opened

58
Q

what happens to the Vm during repolarisation

A

the Vm moves towards the K nernst potential as the potassium channels have opened.

59
Q

where is sodium- amino acid cotransport found?

A

in epithelial cells

60
Q

what happens when phenylalanine is add to a transporter? what does this cause? what does potassium then do?

A

sodium can then be transported, this causes depolarisation. potassium channels then open after several minutes allowing potassium to re eneter and the cell to repolarise.

61
Q

what are the normal intracellular and extracellular sodium conditions?

A

145mM extracellular

15 mM intracellular

62
Q

in the epithelial cell of the thick ascending limb of the loop of henle, how is an osmotic gradient created?

A

apical membrane allows reabsoprtion of NaCl in preference to H2O. there’s an Na/K pump and Cl channel on the basolateral membrane. (apical memb impermeable to water, ammonia and protons)

63
Q

what does the activity of NKCC on the epithelial cell of the thick ascending limb of the loop of henle depend on?

A

it depends upon the inward sodium gradient. if intracellular sodium conc are raised then the activity of NKCC stops.

64
Q

what happens when the transepithelial osmotic gradient of the epithelial cell of the TAL of the LoH is dissipated?

A

it leads to diuresis and increased conc of Na and Cl in urine.

65
Q

in excitable cells under normal conditions what are the usual Ena and Vm? what does this mean?

A

Ena = +60mV
Vm = -70 mV
this means there is a large inward electrical gradient for Na

66
Q

what would happen if intracell concs of Na is increased from 15 to 45mM?

A

there would be a decrease in the inward chemical gradient

67
Q

what would happen if the ENa becomes +30mV

A

as there’s a decrease in the electrical gradient it would mean it takes longer for the potential to develop, meaning there’s problems with proppagation of AP… resulting in slower conductance of action potentials.

68
Q

what governs the control of intracellular Na?

A

the Na/K ATPase

69
Q

how does the Na/k pump work? (7)

A
  • Na enters and binds
  • ATP phosphorylised Atp - adp
  • conformational change
  • na is released
  • K binds to the pump
  • pump is dephosphorylised
  • change in structure and k+ is released from the cell.
70
Q

what is the rate of transport of the na/k pump saturable function of? (2)

A
  • Na intracellularly and K extracellularly

- ATP

71
Q

what is the Na/K pump inhibited by? what does the pump maintain?

A

cardiac glycosides ouabain and digoxin. it maintains the low intracellular Na and high intracellular K

72
Q

what are the two factors in creating the membrane potential? which has a more major role?

A
  1. electrogenic transport
  2. accumulation of intracellular K creates a driving force for k to leave the cell.
    accumulation of intrac k has a more major role. electrogenic transport only contributes to about 20% of the membrane potential.
73
Q

why is Na into the cells generally only by pathways of physiological significance?

A

because the energy expenditure is so great

74
Q

what allows directional transport of Na in the collecting duct?

A

there are amiloride sensitive channels on the apical membrane and a pump on the basolateral memb.
so instead of just recycling there is also directional transport

75
Q

what are the normal conditions of calcium?

A

1mM extracellularly

100 nM intracellularly

76
Q

why is calcium regulation important?

A

because calcium is an important second messanger

e.g in pancreatic acinar cell

77
Q

why is maintaining low intracellular calcium levels so important

A

the gradient is extremely favourable for Ca entry as there is a 10,000 fold chemical gradient and the Eca of calcium is +120

78
Q

what are the two main mechanisms for maintaining low intrac calcium levels?

A

na/ca echanger

and the Ca ATPase

79
Q

what does the Na/Ca exchanger exchange? what is the stiochemistry for this?

A

it exchanges the extrac Na for intracell Ca

3Na: 1Ca

80
Q

what gene and superfamily is the na/ ca exchanger part of? what form is in mammels andhow many of these forms are there?

A

members of the SLC8 gene family
part of the CaCA superfamily
three forms in mammels named NCX1-3

81
Q

why is the spliced elemement important in NCX1-3

A

small changes allow different tissues to regulate in slightly different ways

82
Q

what family are the Ca ATPases part of? what other pump is part of this family?

A

part of the P type ATpase family.

Na/K pump

83
Q

how many types of Ca pumps are there?

what are these three pumps?

A

3
PMCA
SERCA
SPCA

84
Q

what are PMCA pumps?

A

they are plasma membrane calcium pumps

the act to pump Ca across the plasma memb out of the cell

85
Q

what are SERCA pumps?

A

calcium pumps found on the SR and ER

pump Ca out of the cytoplasm into the organnelles that act as calcium stores

86
Q

what are SPCA pumps? what do they also transport?

A

calcium pumps found on the golgi apparatus

also transport Mn2+

87
Q

what are the for types of Ca signalling plasma membrane pathways?

A
  1. Voltage operated Ca channels (VOCC)
  2. Receptor operated Ca channels (ROCC)
  3. Mechanically activated Ca channels
  4. Store operated Ca channels
88
Q

where are VOCCs found and what activates them?

A

found in excitable cells

activated by depolarisation

89
Q

where are ROCCs found and what activates them?

example?

A

found in secretory cells and nerve terminals
activated by the binding of an agonist
e.g NMDA receptors

90
Q

where are mechanically activated Ca channels found?
what do they respond to?
example?

A

found in many cells
respond to cell deformation
e.g stretch activated channels

91
Q

what are SOCC activated by?

A

by the depletion of calcium stores

92
Q

where does the calcium used through SOCC come from?

A

from the ER

93
Q

how many classes of Ca channels are there in store membranes? name them.

A

2
IP3 receptors
Ryanodine Receptors

94
Q

where are IP3 receptors found? what do these receptors activate?

A

they are expressed in most cell types

they activate channels following the binding of IP3

95
Q

what do ryodine receptors do?

what do low concs of ryodine do? high concs?

A

activate channels
low concs activate the channels
high concs inhibit the channels

96
Q

what are the ryodine channels also stimulated by?
what’s the natural activator?
where are these channels generally found?

A

also stimulated by caffeine
natural activator is cADP ribose
found in excitable cells

97
Q

what kind of scale is pH? what does this mean for changes in pH?

A

logarithmic

very small changes in pH result in large changes in proton concentration

98
Q

what can happen to proteins when pH changes? what do these proteins act to do? is this the same for every protein?

A

proteins act to buffer changes in proton concentrations
can lead to changes in; protein charge, protein conformation and function.
no, some proteins are regulated by pH change

99
Q

how does the cell compensate for an increase in protons (acidify)?

A

protons are removed, alkalisation occurs

100
Q

how does the cell compensate for a decrease in protons (alkalisation)?

A

add protons, acidifications

101
Q

how is intracellular pH measured using microelectrodes?

A

2 electrodes V1 and V2,
V2 measures the overall memb potential
V1 measures everything but protons
voltage difference between v1 and v2
the change is proportional to a change in pH.
electrodes calibrated with pH standard. 2 pHs taken and voltage of both is measured. drawa straight line through.

102
Q

what cells are microelectrodes good for?

bad for?

A

big cells such as nerve, muscle, xenopus oocytes

bad for small epithelial cells

103
Q

how is pH measured using fluorescent indicators?

A

cells loaded with an inactive lipid soluble indicator
inside the cell this is activated by enzymes making it lipid insoluble so it can no longer leave the cell.
indicator excited with light of a certain wavelength
amount of emitted fluorescence is measured at a second wavelength, this is proportional to intracellular pH

104
Q

what are three factors involved in the control of intracellular pH?

A
  1. buffering
  2. acid extrusion
  3. acid loading
105
Q

in the ‘model cell’ how does acid extrusion and acid loading occur?

A

acid extrusion - the sodium-proton pump (sodium in, protons out)
Acid loading - the chloride bicarbonate exchanger (Cl in and HCO3 out)

106
Q

what is a pH buffer?

A

a system that moderates the effects of an acid or an alkali load by reversibly consuming or releasing protons

107
Q

what do buffering systems act to do?

A

minimise pH changes to help protect the cell from damage.

108
Q

what is buffering power?

A

the amount of strong base that must be add to a solution in order to raise pH by a given amount

109
Q

can buffers prevent a change in pH?

A

no, they merely minimise the magnitue of change

110
Q

can buffers reverse the change in pH?

A

no recovery is due to acid extrusion/ loading mechanisms

111
Q

what does buffering by proteins depend on?

A

the ability of -COOH or NH2 groups on the amino acids to donate or recieve protons

112
Q

what exchanger is involved in acid extrusion?

what does this rely upon?

A

the na/h exchanger

relies upon the inward Na gradient created by the na/k pump

113
Q

when is the exchanger inactive?

when is it stimulated?

A

inactive when the pH is more alkaline than the setpoint.

the exchanger activity is stimulated at acidic pHs

114
Q

what is Allosteric Modification?

A

when protons other than the one being transported bind to the NHE protein, resulting in a conformational change that increases the activity of the protein

115
Q

what kind of gene is NHE1, what does it have primary roles in?

A

a housekeeping gene, primary roles in intracellular pH regulation and the control of cell volume

116
Q

what is NHE1 inhibited by?

what is the analogue of this which also inhibits? where is it found? what’s different about it?

A

inhibited by low concs of amiloride
it’s anolgue is EIPA which is found in the baso memb of epithelial cells. EIPA doesn’t inhibit other channels it is specific for NHE

117
Q

what exchanger is involved in acid loading?

what family is this part of? what direction is it usually in?

A

the cl/hco3 echanger
it’s part of the anion echanger (AE) family
usually inward movement of Cl in echange for HCO3

118
Q

why does removing HCO3 result in acidification?

A

because when HCO3 is removed, H+ is left behind

119
Q

what is the exchanger modulated by?

A

modulated by pH, there’s a low activity at acidic pHs which increased as the pH gets more alkaline.

120
Q

how many subtypes are there in the anion exchanger family?

A

there are 4 subtypes

physiology and pharmacology (7 decks)

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