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BMS 242 - Core Phys/pharm > Cell homeostasis > Flashcards

Cell homeostasis Flashcards

1
Q

What gradient is important to drive secondary active processes in the cell?

A

The Na+ gradient (low intracellular and high extracellular

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2
Q

What is the concentration of Na+ INSIDE the cell?

A

15mM

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3
Q

What is the concentration of Na+ OUTSIDE the cell?

A

150mM

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4
Q

Which transport protein keeps intracellular Na+ low?

A

Na/K ATPase (pump)

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5
Q

Describe the apical and basolateral membranes of the epithelial cell in the thick ascending limb

A

Basolateral membrane:
1) Na/K ATPase keeps intracellular Na low

2) K+ channel
3) CLCK (Cl- out)

Apical membrane:
1) NKCC (Na, K, Clx2 in)

2) ROMK (K out)

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6
Q

In the thick ascending limb, what produces the driving force for NKCC?

A

Na/K ATPase - keeping intracellular Na+ low

ROMK - recycles out K+

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7
Q

In the thick ascending limb, what happens if [Na+] is increased inside the cell?

A

1) NaCl reabsorption inhibited as NCKK can’t work
2) Osmotic gradient across the thick ascending limb decreases
3) Less water absorbed (follows Na)
4) Increased salt wasting and diuresis

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8
Q

What is Ena?

A

+60mV

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9
Q

What happens, with regards to the action potential, if [Na+] is increased INTRACELLULARILY?

A

1) Ena becomes ~30mV
2) Reduced electrochemical gradient and driving force for Na+ into the cell
3) Take LONGER for the action potential to develop and the PEAK will not be as high
4) Slower conduction of the action potential and problems with propagation

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10
Q

What is the extrusion of 3Na and uptake of 2K by Na/K ATPase coupled to?

A

The hydrolysis of ONE ATP

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11
Q

What is the model of Na/K pump action?

A

1) Na+ binds to cleft on the INTERNAL side of the pump
2) Hydrolysis ATP –> ADP
3) Phosphorylation of the pump - causing a conformational change
4) Binding cleft exposed to the OUTSIDE of the cell
5) Na+ leaves and K+ binds
6) Pump loses phosphate group - returns to its original confirmation
7) Cleft exposed to INTERNAL environment
8) K+ leaves cleft and Na+ bind

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12
Q

What does the rate of transport of the Na/K ATPase pump depend upon?

A

1) SATURATION - rate is saturable by [Na]i and [K]o

2) Metabolic rate of the cell - rate is saturable by [ATP]

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13
Q

What inhibits the Na/K pump?

A

Cardiac glycosides:

  • Ouabain
  • Digoxin
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14
Q

How does Na/K maintain a the inside of the cell to be NEGATIVE?

Which factor plays more of an importance?

A

1) Electrogenic transport: 3+ out, 2+ in
- Makes inside more negative

2) Accumulation of K+ inside the cell (by Na/K ATPase transporting them in)
- Driving force for K+ to leave through OTHER channels
- Make intercellular more negative
- MAJOR FACTOR

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15
Q

What allows directional transport in the collecting duct?

A

Amiloride sensitive channels (NHE1) are on the APICAL membrane
Na/K ATPase is on the basolateral membrane

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16
Q

What produces depolarisation in excitable cells?

What is this recycled by?

A

Na+ entry

Recycled by the Na/K ATPase

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17
Q

What does Na+ drive in the kidney?

A

The REABSORPTION of many OTHER ions

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18
Q

What is the concentration of INTRACELLULAR Ca2+?

A

100nM

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19
Q

What is the concentration of EXTRACELLULAR Ca2+

A

1mM (1,000,000nM)

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20
Q

What is the difference between intracellular and extracellular concentration of Ca2+?

A

10,000 fold difference

Extracellular concentration in 10,000 more than intracellular concentration

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21
Q

What is Eca?

A

+120mV

Double that of Na and +61mV

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22
Q

Why is Ca2+ important?

A

SECONDARY messenger in many signalling pathways

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23
Q

What does Ca2+ release from stores cause in the pancreatic acinar cell?

A

Fusion of vesicles to the membrane and release of enzymes

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24
Q

What 2 mechanisms help to keep Ca2+ concentration low?

A

1) Na/Ca Exchanger

2) Ca2+ ATPase

25
Q

What does the Na/Ca exchanger do normally?

How can this differ?

A

Exchange 3 extracellular Na for 1 intracellular C (Na in, Ca out)

Differs depending on the gradients set up - eg. this is reversed in the heart (Na out Ca in)

26
Q

How can a 10 fold Na+ gradient keep Ca2+ in the cell so low when the Ca2+ gradient it 10,000 fold?

A
  • 3 Na+ for every 1 Ca+
  • Means the effect of the Na+ gradient is CUBED - giving a 1,000 fold Na+ gradient
  • Membrane potential gives another 10-fold Na+ gradient
  • 1,000 x 10 = 10,000
  • Matches the 10,000 fold Ca+ gradient
27
Q

What family is the Na/Ca exchanger part of?

A

SLC8 family

CaCA SUPERFAMILY

28
Q

How many forms of the Na/Ca exchanger exist in mammals and what are they called?

A

Three:

NCX1
NCX2
NCX3

29
Q

What family is the Ca pump a family of?

What transport protein is also in this pump?

A

P-type ATPase

Na/K pump is also in this family

30
Q

What do ALL the Ca pumps (Ca ATPase) act to do?

A

REMOVE Ca2+ from the cytoplasm

31
Q

How many of the 3 Ca pumps can be present in a given cell?

A

3

32
Q

What are the 3 types of Ca pump?

Where are they found?

A

1) PMCA (plasma membrane)
2) SERCA (smooth endoplasmic reticulum or sarcoplasm)
3) SPCA (golgi apparatus)

33
Q

What does SERCA act to do?

A

Pump Ca2+ OUT of the CYTOPLASM

Into organelles which act as calcium STORES

34
Q

What do calcium stores do?

A

Store Ca2+ and release it into the cell when there is a trigger event

35
Q

What does PMCA act to do?

A

Pump Ca2+ OUT of the cytoplasm across the cell wall

36
Q

Which Ca pump can also transport Mn (manganese)?

A

SPCA

37
Q

What are the 4 plasma membrane pathways for Ca2+?

A

1) VOCC (voltage operated calcium channels)
2) ROCC (receptor operated calcium channels)
3) Mechanically activated Ca+ channels
4) SOCC (store operated calcium channels)

38
Q

What activates VOCC?

A

Depolarisation of the membrane

39
Q

What activates ROCC?

A

Binding of an agonist

40
Q

Where are VOCC found?

A

In excitable cells

41
Q

Where are ROCC found?

A

In nerve terminals and secretory cells

42
Q

What activates mechanically activated Ca2+ channels?

A

Deformation of the membrane

43
Q

Where are mechanically activated Ca2+ channels found?

A

In MANY cells

44
Q

Where are SOCC found?

A

In the CELL membrane

45
Q

What activates SOCC?

A

Depletion of Ca+ stores in the cytoplasm

46
Q

What do SOCC act to do?

A

Replenish the Ca+ stores in the cytoplasm

47
Q

What RECEPTORS are present in Ca2+ store membranes?

Which is the most common?
Where is the other receptor present?

A

1) IP3 receptors
- Most common

2) Ryanodine receptors
- Excitable cells

48
Q

What is the function of the IP3 and Ryanodine receptors present in Ca2+ store membranes?

A

To get Ca2+ from the stores into the cytoplasm

Happens in response to a signal

49
Q

What activates the IP3 channel in the store membrane?

A

Binding of IP3

50
Q

What activates the Ryanodine channel in the store membrane?

What is the NATURAL activator

A
  • LOW concentrations of Ryanodine
  • Caffeine
  • cADP ribose (natural activator)
51
Q

What inhibits the Ryanodine channel in the store membrane?

A

HIGH concentrations of Ryanodine

52
Q

What happens when PLC is activated by a receptor?

A

1) Splits PIP2 into IP3 and DAG
2) IP3 binds to IP3 receptors on the Ca2+ store membrane
3) Ca2+ is released from the store into the cytoplasm - emptying the store

53
Q

What occurs when the Ca2+ store is empty?

A

1) Signalling between the empty store and SOCC in the cell membrane
2) STIM Ca2+ binding state changes - STIM undergoes conformational change (dimer –> multimeric)
3) Further conformational change allows the multimeric STIM to tether and bind to the PM membrane
4) STIM interacts with Orai Ca2+ channels (SOCC) in the PM membrane
5) Orai channels open and Ca2+ move into the store
6) Complex feedback prevents Ca2+ from leaving the store
7) Once store is replenished - signalling stops

54
Q

What is STIM?

A

A transmembrane spanning domain

Spans the SER (Ca2+ store)

Normally binds Ca2+ inside of the store

55
Q

Where are Orai Ca2+ channels present?

A

In the plasma membrane

56
Q

How does an empty store communicate with SOCC in the membrane?

A

Thought to be through tethering

57
Q

What is the function of the Orai Ca2+ channel?

A

To allow Ca2+ INTO the store - to replenish it

It is a SOCC

58
Q

Where is Orai Ca2+ channel present?

A

In the PLASMA membrane

BMS 242 - Core Phys/pharm (13 decks)

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