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Membranes and Receptors > Session 5 - Control of cytosolic Ca > Flashcards

Session 5 - Control of cytosolic Ca Flashcards

1
Q

What does establishing and maintaining the Ca gradient rely on?

A
  • Relative impermeability of the PM

- Dependant upon the cells ability to expel Ca2+

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2
Q

What determines a cells impermeability to Ca?

A

-Open/closed state of ion channels

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3
Q

What is PMCA?

A

-A primary active transporter in cell membranes which uses ATP hydrolysis to expel Ca

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4
Q

What feedback system does PMCA work on?

A

-[Ca]i increases ->Ca binds to CaM-> Ca-CaM binds to PMCA-> Ca removed

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5
Q

What is the affinity and capacity of PMCA?

A
  • High affinity
  • Low capacity
  • Removes residual Ca
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6
Q

What is NCX?

A
  • Na-Ca-exchanger
  • Secondary active transporter in plasma membrane which uses the Na concentration gradient to drive Ca out of the cell
  • 3Na in for every Ca out (antiport)
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7
Q

Describe the affinity and capacity of NCX

A

-Low affinity
-High capacity
Main remover of high [Ca]i

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8
Q

What are Ca buffers?

A

-Buffers in the body contain Ca-binding proteins which cause Ca to diffuse more slowly across PM by binding to Ca and preventing it diffusing across

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9
Q

What are the 4 main factors of cells which provide the ability to control Ca?

A
  • PMCA
  • NCX
  • Ca buffers
  • Intracellular stores
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10
Q

In what two ways can Ca influx across the PM?

A
  • Voltage-gated Ca channels

- Ligand-gated Ca channels

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11
Q

What is SERCA?

A

-Primary active transporter which uses energy from ATP hydrolysis to pump Ca against its concentration gradient into SR when [Ca]i are high

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12
Q

Describe the affinity and capacity of SERCA

A
  • High affinity

- Low capacity

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13
Q

How is Ca released from the SR?

A
  • Via IP3 ligand-gated Ca channels

- Via Ryanodine receptors (CIRC)

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14
Q

Describe how Ca is released from SR via a1 in vascular smooth muscle cells

A
  • NA binds to a1- adrenoreceptors, Gaq dissociates and activates PLC
  • PLC cleaves PIP2 to IP3 and DAG
  • DAG regulates PKC
  • IP3 binds to IP3R on SR, opens the ion channel
  • Ca influx into cell
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15
Q

Describe Gas pathway

A
  • Gas dissociates and stimulates AC
  • AC converts ATP to cAMP
  • cAMP increases the activation of PKA
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16
Q

Describe Gai pathway

A
  • Gai dissociates and inhibits AC
  • cAMP decreases
  • Decreased activation of PKA
17
Q

What do Gbg subunits do?

A

-Open/close ion channels

18
Q

Describe Ca-induced Ca-release

A
  • Intracellular Ca rises
  • Ca binds to ryanodine receptors on SR
  • Ligand-gated Ca channel opens rapidly releasing Ca into cell
19
Q

Where is the main site of CIRC? Why?

A

-Cardiac myocytes in response to Ca entry through voltage-gated Ca channels to maintain plateau by releasing intracellular calcium -> contraction

20
Q

When does NCX reverse directions?

A
  • During depolarisation as intracellular Na becomes high

- 3Na out 1Ca in

21
Q

What is the minor contributor of Ca handling in cardiac myocytes?

A

-NCX

22
Q

What is the major contributor to Ca handling in cardiac myocytes?

A

-SERCA

23
Q

Where are non-rapidly releasing stores of Ca within cells?

A

-Mitochondria

24
Q

When will mitochondria take up Ca?

A

-When [Ca]i is high

25
Q

How do mitochondria participate in normal Ca signalling?

A

-They are in a cellular arrangement where they will be exposed to high levels of Ca

26
Q

Describe mitochondrial uptake of Ca

A

-Uniporter which is low affinity and high capacity

27
Q

How is [Ca]i returned to normal?

A
  • Ca removal

- Intracellular store refil

28
Q

How are intracellular stores of Ca refilled?

A
  • SERCA and mitochondria to recycle cytosolic Ca
  • In excitable cells there can be voltage-gates Ca2+ sequestering whereby voltage-gated channels open and the Ca influx is sequestered
  • Capacitative Ca2+ entry
29
Q

What is capacitative Ca2+ entry?

A
  • Capacitative/store operated channels
  • SR signals depletion of Ca and SOC open to allow Ca2+ utake
  • Regulated by specific proteins STIM (an ER located Ca2+ sensor) and ORAI( a PM channel) which interact to activate SOC
30
Q

Why is it important to have mechanisms to move Ca in and out of cells?

A
  • Ca cannot be metabolised and high doses are toxic
  • Ca needs to be at a low concentration within cells so there is a large concentration gradient -> movement of small amounts of Ca cause big changes in Ca intracellulaar concentration
31
Q

Describe Gaq pathway

A
  • Gaq activates PLC
  • PLC cleaves PIP2 into IP3 and DAG
  • IP3 acts on IP3R and is a second messenger
  • DAG activates PKC

Membranes and Receptors (13 decks)

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