lecture 1 (week 8)

Question 1

what is the normal concentration of sodium in the ECM and intracellularly?

Answer 1

140mM in the ECM and 10mM intracellularly. (higher conc. of sodium in the blood/ECM than intracellularly)

Question 2

what is the normal concentration of potassium in the ECM/blood and intracellularly?

Answer 2

5mM in the ECM/blood and 140mM intracellular. (higher conc. of potassium inside the cell than outside)

Question 3

is the intracellular environment usually negative or positive?

Answer 3

negative - because of many things including the negative nature of DNA.

Question 4

why is the active transport system of sodium and potassium called the sodium pump?

Answer 4

since the extrusion of sodium takes place against a steep electrochemical gradient (positive ion moves from negative intracellular environment to positive ECM) and concentration gradient.

Question 5

what is the structure of the sodium pump?

Answer 5

alpha, beta tetramer trans-membrane protein channel.

Question 6

what is the structure of the beta sub units of the sodium pump?

Answer 6

they are highly glycosylated

Question 7

what is the structure and function of the alpha sub unit of the sodium pump?

Answer 7

the alpha sub unit has 2 ATP binding sites intracellularly as well as 3 sodium binding sites. It also has 2 cardiac glycoside binding sites extracellularly which are also 2 potassium binding sites.

Question 8

explain the sequence of events involved in the sodium pump.

Answer 8

ATP binds to the binding sites intracellularly, along with 3 sodium ions. 2 potassium ions bind extracellular. The ATP is hydrolysed into ADP and a phosphate. The phosphate binds to the alpha dimer and changes the conformation of the protein. this relates the sodium to the ECM and the potassium to the intracellular environment. The phosphate is released from the sodium and pump and the conformation changes back.

Question 9

how many sodium pumps do most cells have?

Answer 9

1 million. However, the number of sodium pump varies with the type of cell. e.g. kidney cells have more sodium pumps.

Question 10

what is the Km for sodium to be transported across the membrane?

Answer 10

20mM

Question 11

what is the Km for potassium to be transported across the membrane?

Answer 11

1mM

Question 12

how does the concentration of intracellular sodium affect the rate of the (Na + K)ATPase enzyme?

Answer 12

the intracellular concentration of sodium is usually 10mM which is less than the Km of 20mM. However the extracellular potassium concentration is usually 140mM which is much higher than the Km of 1mM. Therefore the limiting factor is the concentration of intracellular sodium, which controls the rate of the sodium pump. (removing the potassium or lowering it to a level near the Km also affects the rate)

Question 13

what is the rate of the sodium pump usually?

Answer 13

100 times per second

Question 14

what is another name for cardiac glycosides?

Answer 14

digoxin

Question 15

what happens when there is a decrease in the concentration of potassium?

Answer 15

there is an increased affinity between cardiac glycosides and the sodium pump. (therefore it is always important to know the concentration of potassium in a patient’s blood before administering cardiac glycosides(or digoxin))

Question 16

what is the therapeutic index and how is it calculated?

Answer 16

ratio of therapeutic effect to toxic effect. Calculated by: dose producing toxicity in 50% of population/ min. effective (therapeutic) dose for 50% of population

Question 17

what is the therapeutic index for digoxin?

Answer 17

2:1

Question 18

what is hypokalaemia and what are the symptoms?

Answer 18

low levels of potassium in the blood (less than 3.5mM) - abnormal heart rhythms. Moderate (2.5-3.0) - muscle damage (rhabdomyolysis). Severe (less than 2.5) - muscle weakness or spasms and paralysis

Question 19

what is hyperkalaemia and what are the symptoms?

Answer 19

high levels of potassium in the blood (more than 5.5) moderate (6.1-6.9). Severe (more than 7.0). Symptoms: nausea, palpitations and muscle weakness.

Question 20

what is normokalaemia?

Answer 20

normal levels of potassium in the blood (3.6-5.2)

Question 21

what is a diuretic?

Answer 21

a substance which increases the urine output by the kidneys by DIURESIS inhibiting a sodium, potassium reabsorber, therefore less water is reabsorbed. (this is important because potassium is not being reabsorbed so levels of potassium could drop to dangerous levels)

Question 22

what are the conditions which diuretics are used to treat?

Answer 22

high blood pressure and excessive fluid retention.

Question 23

what are some examples of diuretics?

Answer 23

furosemide

Question 24

what is digibind?

Answer 24

a drug which rapidly binds to digoxin causing it to dissociate from the sodium pump which can reverse digoxin toxicity.

Question 25

what is primary active transport?

Answer 25

the direct coupling of the hydrolysis of ATP to molecular movement to move substances against the concentration gradient

Question 26

what is secondary active transport?

Answer 26

uses the energy stored in th sodium gradient (generated by the sodium pump) to drive molecular transport against the electrochemical gradient.

Question 27

which way are molecules moved by the sodium gradient?

Answer 27

both in and out. The energy stored in the sodium gradient can be used to drive molecules into the cell and out of the cell.

Question 28

what is movement of molecules out of the cells generated by the energy stored in the sodium gradient called?

Answer 28

outwardly directed secondary active transport

Question 29

what are facilitated glucose transporters?

Answer 29

membrane transporters which work independently to move glucose into the cell. (This works because there is usually a low concentration of free glucose molecules inside the cell as most glucose is found in the form of glucose 6 phosphate inside the cell.) e.g. GLUT1-5

Question 30

what is sodium dependant glucose transport - secondary active co-transport?

Answer 30

the movement of glucose into the cell which is dependant on the movement of sodium into the cell. e.g. SGLT1 and 2.

Question 31

what type of glucose transporter is usually found on the apical surface of epithelial cells?

Answer 31

sodium dependant glucose transporters.

Question 32

what type of glucose transported are usually found on the basal surface of epithelial cells?

Answer 32

facilitated glucose transporters.