Active Transport: The Sodium Pump

Question 1

Why is it called the sodium pump?

Answer 1

Since the extrusion of Na+ takes place against a steep electrochemical gradient (concentration and electrical) the active transport system is called the sodium pump.

Question 2

What are the structures of the sodium pump?

Answer 2

+ Extracellular surface
+ Intracellular surface
+ Cardiac glycoside binding sites
+ ATP binding sites

Question 3

What are features of the sodium pump?

Answer 3

+ α2β2 tetramer, MW 270000 α95000 β 4000

+ ATP must be available intracellulary

+ Cardiac glycosides only inhibit from the extracellular surface

+ Na+ ions bind internally (3 per α)

+ K+ ions bind externally (2 per α)

+ Most cells have around 1 million sodium pump sites

Question 4

What is the sodium pump equation?

Answer 4

[3Na+]i +[2K+]o [3Na+]o +[2K+]i

Question 5

What are some features of the sodium/(Na+ + K+)ATPase pump reaction?

Answer 5

+ ATP is hydrolysed to ADP by the enzyme (Na+ + K+)ATPase

+ Reaction occurs 100 times per second

+ Can be inhibited by removing [K+]o

+ Can be stimulated by increasing [Na+]i

Question 6

What is the effect of a decrease in [K+]o on digoxin inhibition of the sodium pump?

Answer 6

+ An increased affinity between cardiac glycosides and the sodium pump

Question 7

What is the therapeutic index?

Answer 7

+ A ratio: the larger the therapeutic index, the safer the drug

+ Comparison of the amount of a therapeutic agent that causes the therapeutic/clinically desired effect to the amount that causes toxicity
- dose producing toxicity for 50% of the population/Minimum effective dose for 50% of the population

Question 8

What is Remifentanil used for and what it its TI?

Answer 8

+ Patient controlled analgesia during labour (synthetic opiod)

+ 33000:1

Question 9

What is Diazepam used for and what it its TI?

Answer 9

+ Sedative

+ 100:1

Question 10

What is Ethanol used for and what it its TI?

Answer 10

+ Sedative

+ 10:1

Question 11

What is Digoxin used for and what it its TI?

Answer 11

+ Congestive heart failure

+ 2:1

Question 12

What does it mean if a drug has a low TI?

Answer 12

+ May require drug monitoring both to achieve therapeutic levels and to minimize toxicity

Question 13

What is hypokalaemia?

Answer 13

Lower than normal potassium levels in the blood (mEq/L)

+ Less than 3.5

+ Moderate (2.5 - 3.0)

+ Severe (less than 2.5)

Question 14

What is normokalaemia?

Answer 14

Normal potassium levels in the blood (mEq/L)

+ 3.6 - 5.2

Question 15

What is hyperkalaemia?

Answer 15

Higher than normal potassium levels in the blood (mEq/L)

+ More than 5.5

+ Moderate (6.1 - 6.9)

+ Severe (more than 7.0)

Question 16

What is the role of potassium?

Answer 16

+ A nutrient critical to the function of nerve and muscle cells

+ Crucial to heart function

+ Plays key role in skeletal/smooth muscle contraction

+ Important for normal digestive and muscular function.

Question 17

What are the symptoms of hypokalaemia?

Answer 17

+ Abnormal heart rhythms
+ Muscle damage (rhabdomyolysis)
+ Muscle weakness or spasms
+ Paralysis

Question 18

What are the symptoms of hyperkalaemia?

Answer 18

+ Nausea
+ Palpitations
+ Muscle weakness

Question 19

What condition will lead to an increase in digoxin binding?

Answer 19

Hypokalaemia

Question 20

What do diuretics do?

Answer 20

Increase urine output by the kidney (promote diuresis)

Question 21

What can diuretics be used as a treatment for?

Answer 21

+ High blood pressure

+ Excessive fluid retention

Question 22

What are the side effects of loop diuretics such as Furosemide?

Answer 22

Increase urinary excretion of potassium

Question 23

What might happen to patients on digoxin who start diuretics such as furosemide, and why can this contribute to digoxin toxicity?

Answer 23

They may become hypokalaemic

+ Reduction in competition between K+ and digoxin (due to increased urinary excretion of K+) results in increased digoxin binding to sodium pump

+ Due to the narrow therapeutic index, patient develops digoxin toxicity

Question 24

What is the emergency treatment for digoxin toxicity?

Answer 24

+ Administer a digoxin binding antibody such as digibind

+ Rapidly binds to the digoxin

+ Digoxin dissociates from sodium pump reversing toxicity

Question 25

What is primary active transport?

Answer 25

+ Utilises energy in form of ATP to transport molecules across a membrane against their concentration gradient

Question 26

What is secondary active transport?

Answer 26

+Utilises energy stored in the Na+ gradient (generated by the sodium pump) to drive molecular transport against the electrochemical gradient

Question 27

What are the types of glucose transporters?

Answer 27

+ GLUT1: basal uptake in placenta and brain

+ GLUT2: transepithelial transport, β cells

+ GLUT3: basal uptake in brain

+ GLUT4: skeletal muscle (insulin dependent)

+ GLUT5: intestinal absorption of fructose

Question 28

What are glucose transporters and what kind of transport is involved?

Answer 28

+ Wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane

+ Facilitated transport/secondary active co-transport

Question 29

Which glucose transporter is insulin dependent?

Answer 29

GLUT4

Question 30

What kind of transport is involved with the sodium calcium exchanger?

Answer 30

Secondary active counter transport