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BIO304 > Lecture 5 > Flashcards

Lecture 5 Flashcards

1
Q

Na+/K+ ATPase exchange pump (Sodium Potassium Pump)

A

Maintains Na+ and K+ gradients across the cell membrane
- Pumps 3 Na+ out of the cell for every 2 K+ pumped in

Consumes energy (ATP–>ADP) - Active Transport

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2
Q

Structure of the Na+/K+ ATPase exchange pump

A

Dimeric structure of one alpha (α) subunit and one beta (β) subunit

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3
Q

Human Sodium Potassium Pumps

A 
Humans have 4 α genes:
• ATP1A1 (α1): Ubiquitous expression
• ATP1A2 (α2): Muscle and nervous tissue
• ATP1A3 (α3): Neurons
• ATP1A4 (α4): Testis

Humans have 4 β genes:
• ATP1B1 (β1): Ubiquitous expression
• ATP1B2 (β2): Muscle and brain
• ATP1B3 (β3): lung, testis, skeletal muscle, and
liver
• ATP1B4 (β4): Divergent function in placental mammals (i.e. nuclear); still associates with α subunit in fish, avian, and amphibian species

**Don’t need to memorize gene numbers or types, just know that there are several genes with different expression patterns*

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4
Q

Sodium Potassium Pump and RMP

A
  • The sodium-potassium exchange pump is “electrogenic”
  • Every transport cycle results in the net extrusion of 1 positive charge
  • Thus, the pump contributes to the negative RMP of the cell
  • This contribution is -6 to -11 mV
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5
Q

R.C. Thomas’ experiment on the Electrogenic Nature of the Sodium Potassium Pump

A

• Impaled a single large snail neuron with 5
electrodes!
• The Li+ and Na+ electrodes inject those ions into the cell, if one injects the other removes cations to compensate
• Injection of Na+, but not Li+, causes the membrane potential to drop
• Blocking the pump with ouabain blocks the Na+ effect • External K+ is also required

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6
Q

Oubain

A

Na+/K+ ATPase blocker

α3 subunit is 1000-fold more sensitive

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7
Q

Rapid Onset Dystonia Parkinsonism (ROPD)

A

Mutations in α3 subunit

can be artificially created by injecting Oubain into the brain

can also be triggered by stress

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8
Q

Why Ca2+ is good

A
  • Binds oxygen atoms
  • Causes conformational changes in proteins (good for signalling or activating mechanical processes)
  • Vesicle exocytosis, muscle contraction, activating other ion channels)
  • Due to toxicity, kept at very low levels in cells, making it ideal as a transient signalling molecule
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9
Q

Why Ca2+ is bad

A

• It precipitates phosphates (CaPO4), which can accumulate and become toxic
to cells
• Cannot be chemically altered for neutralization

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10
Q

[Ca2+]in vs. [Ca2+]out

A

[Ca2+]in

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11
Q

Ca2+ Pumps

A

2 types of Ca2+ pumps
• Plasma membrane calcium ATPase (PMCA)
• Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)

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12
Q

PMCA Pump

A

1 Ca2+ ion pumped out of the cell per cycle (hydrolysis

of a single ATP molecule)

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13
Q

Human PMCA Pumps

A

Humans have 4 α genes
• ATP2B1 (PMCA1): Brain/Ubiquitous – lethal if mutated
• ATP2B2 (PMCA2): Brain and muscle – hearing loss and balance
• ATP2B3 (PMCA3): Brain and muscle
• ATP2B3 (PMCA3): Broad distribution – male infertility
* Don’t need to memorize gene numbers or types*

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14
Q

SERCA Pump

A

2 Ca2+ ions pumped into the SR/ER per cycle

hydrolysis of a single ATP molecule

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15
Q

Human SERCA Pumps

A

Humans have 3 α genes
• ATP2A1 (SERCA1): Muscle contraction
• ATP2A2 (SERCA2): Muscle contraction
• ATP2A3 (SERCA3): Non-muscle, but expressed in
cardiomyocytes
Don’t need to memorize subunit genes or types

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16
Q

Speed of Ca2+ Pumps

A

SERCA (2 Ca2+) and PMCA (1 Ca2+) are sluggish at removing Ca2+

17
Q

Speed of Ca2+ Exchangers

A

NCX and NCKX exchangers remove Ca2+ much more quickly

18
Q

NCX and NCKX exchangers

A

• Exchangers do not hydrolyze ATP as energy source for moving ions against
their gradients
• Exchangers consume energy from existing ion concentration gradients to move other ions “uphill” against their gradients

19
Q

NCX: • Na+ Ca2+ exchanger (a.k.a. sodium-calcium antiporter)

A

NCX uses the Na+ gradient
• 1 Ca2+ out for 3 Na+ in
• Most widely distributed sodium-calcium exchanger

20
Q

NCX can operate in reverse

A
  • Both Na+ and Ca2+ want to get into the cell
  • Whichever ion experiences the strongest inward full wins
  • In order for Na+ to win, it’s charge x driving force must be greater than that for Ca2+
  • Otherwise Ca2+ wins and it gets to go in the cell
21
Q

NCKX: Na+-Ca2+-K+ exchanger

A

Even better at removing cytosolic Ca2+!!

  • Uses sodium and potassium gradients to remove Ca2+
  • 4 Na+ in and 1K+ out for 1 Ca2+ out (+74 mV for Ca2+ to move inward!)

Reverses at +75mV

22
Q

NCX Structure

A

9 transmembrane segments

23
Q

NCKX Structure

A

11 transmembrane segments

N-terminus is cleaved

24
Q

Cl- transport in Immature Neurons

A

more [Cl-]in than [Cl-]out

25
Q

Cl- transport in Mature Neurons

A

more [Cl-]out than [Cl-]in

26
Q

How do you end up with more [Cl-]in?

A

Cotransporters use the Na+ gradient to

move Cl- into the cell

27
Q

NCC (Na+/Cl- cotransporter)

A

transports 1 Na+and 1 Cl- into the cell

Electrically neutral

28
Q

NKCC (Na+/K+/Cl- cotransporter)

A

transport 1 Na+, 1 K+ and 2 Cl- into the cell

Electrically neutral

29
Q

NCC in Mammals

A

have 1 NCC gene

30
Q

NKCC in Mammals

A

have 2 NKCC genes

31
Q

How do you end up with less [Cl-]in?

A

Cotransporters that use the K+ gradient move Cl- out of the cell

32
Q

KCC: (K+/Cl- cotransporter)

A

transport 1 K+ and 1 Cl- out of the cell

Electrically Neutral

If you want to inhibit (hyperpolarize) a neuron via Cl- channel activation, you need KCC to produce [Cl-]in

33
Q

KCC in Mammals

A

4 KCC genes
• SLC12A4(KCC1) • SLC12A5(KCC2) • SLC12A6(KCC3) • SLC12A6(KCC4)

Don’t need to memorize subunit numbers or types

34
Q

Cl- co-transporters and pH regulation

A
  • Na+-dependent Cl-/HCO3- exchange system uses the Na+ gradient to move bicarbonate into the cell and protons out
  • HCO3- is part of a physiological buffering system crucial in the nervous system, where there is little tolerance for fluctuation in pH

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

  • ↑ in cytoplasmic H+ promotes H+ efflux and HCO3- influx
  • ↑ in HCO3- then shifts the equitation to the left, further neutralizing cytoplasmic pH

BIO304 (15 decks)

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