1.1 Ion Channels And The Na/Ca Exchanger

Question 1

What are the properties of ion channels?

Answer 1

• Ion movement is always down electrochemical gradient
• Movement is fast, 10^7 ions per second per channel
• Channels are selective
• Pore alternates between open and closed states- GATING

Question 2

What is gating of a channel controlled by?

Answer 2

• Voltage gated- membrane potential
• Ligand gated- binding of a chemical
• Mechanical gating- membrane deformation

Question 3

What is the reversal potential?

Answer 3

The reversal potential is the potential at which no net current flows when the channel is in its open state.

Question 4

What determines the reversal potential of a ion channel?

Answer 4

The reversal potential depends on the relative permeability of the ion channel

Question 5

how can we model the flow of ions through channels?

Answer 5

1. Ions will only flow when the channel is open
2. Ions only flow down their electrochemical gradient
   Can use I=G.V or also G=1/R

An open channel can be compared to a resistor and thus we can use ohms law
However we can replace V with electrochemical gradient
With V-E rev can be found by I (pA)= Y(V-E rev)
Y= channel conductance in pS

Question 6

How do we measure single channel currents experimentally?

Answer 6

Single channel currents can be measured using excise patches.

Question 7

What are the two types patch clamp recordings?

Answer 7

You can have inside out patch which is where the solution in the pippet is in contact with the extra-cellular membrane while the solution in the recording chamber baths the cytoplasmic membrane.

Question 8

What does a single channel i-V curve show?

Answer 8

Open channel current over voltage, this is different to whole cell IV plots, which are an average current over time.

Question 9

What is the structure off the NCX?

Answer 9

The NCX exchanger is made up of 4 a repeats to form 4 ion binding sites 3 for Na+ and 1 for Ca2+

Question 10

Which direction do the ions travel when NCX is operating in its forward mode?

Answer 10

1 Ca2+ out and 3 Na+ in

Question 11

What direction do the ions flow when NCX is working in its reverse mode?

Answer 11

3 Na out for 1 Ca2+ in

Question 12

What does reversal potential for the NCX exchanger mean?

Answer 12

The reversal potential is the potential at which the NCX exchanger switch’s to its reverse mode.

Question 13

Why can you measure current due to the activity of NCX?

Answer 13

The NCX removed 1 Ca2+ for every 3 Na+ let in so there is a net movement of charge.

Question 14

At typical resting potiential all of -80 mV and typical Na + conc what direction is NCX running?

Answer 14

Inwards?

Question 15

At 0 mV (during the platue phase of cardiac cycle) what direction is the NCX running?

Answer 15

IDK

Question 16

Why does Encx varying during an AP?

Answer 16

As intracellular NA and
Ca2+ is changing.

Question 17

What’s do the different parts of the CV system do?

Answer 17

Heart- forces blood a round the body
Arterial system- Distrubutes blood and acts as a pressure reservoir
Capillaries - transfer metabolites and waste between blood and tissues.
Venous system - blood storage reservoir and return route.

Question 18

What are the primary functions of the CVS

Answer 18

1.Carry metabolites to and waste from the tissues.
2. Communication via hormones.
3.involved in heat regulation.
4.regulates pH of ECF and osmotic balance.

Question 19

What are the stages of the cardiac cycle?

Answer 19

1.Atrial systole- opens atrioventricular valves
2.Ventricualr systole - Isovolumetric stage all valves closed.
3. Ventricualr systole - ejection phase - atria refill semiluar valves open as blood pumped to lungs and around body.
4. Ventricualr diastole- isovolumertric phase, all valves closed.
5. Ventricular diastole- rapid refilling of ventricles

Question 20

What happens to the relative durations of systole and diastole as heart rate increases

Answer 20

They both decrease but relative reduction of systole is much lower than that of diastole to allow for Ventricualr refilling.

Question 21

What is Starlings Law of the heart?

Answer 21

Starlings law states that the greater the stretch of the ventricle in diastole, the greater the stoke work achieved in systole.
The energy of contraction is proportional to the initial length of the cardiac muscle fibre.

Question 22

Why do cardiac myocytes operate within the acesseding phase of the length tension curve?

Answer 22

Cardiac muscle has a parallel elastic component which limits the sarcomere length to that of the rising portion of the length-tension curve, thins is a protein called titin.

Question 23

Why is there a relationship between contractile strength and streach of the filament?

Answer 23

Too close then the thick filaments are compressed. Ideally in middle.
Too stretched and there is no cross bridge cycling as actin can’t reach myosin.

Question 24

What happens to the proportion of cross bridges activated by at a given [Ca2+] during stretch?

Answer 24

More cross bridging at a given Ca2+ concentration with increasing stretch, via an unknown mechanism, although titin seems to be involved, as more complete mutant titin is causes less of a sensitivity response to Ca2+ compared to WT.

Question 25

What is Laplace’s Law?

Answer 25

For a hollow sphere pressure is proportional to the wall tension and inversely porptional to the internal radius.

Question 26

What are the consequences of Starlings law?

Answer 26

Increase in diastolic volume increases ventricuar fibre length and there fore force of contraction. This allows for the balancing of Left and right ventricles output.

Question 27

What are the consequences of Laplace’s law?

Answer 27

Helps late ejection as the ventricular radius is decreasing
Opposes starlings law as the larger the end diastolic volume the lower the efficiency of the heart as at a given tension cardiac muscle produces less pressure. In healthy people starlings law dominates. Failing hearts have higher distension so more Laplace’s law.

Question 28

Where can we control the CVS ?

Answer 28

Cardiac output can be controlled
Local circulation can be controlled by constricting blood vessels.

Question 29

How is the heart controlled?

Answer 29

There are two groups of cardiac control, intrinsic control such as starlings law and the SA node, extrinsic control is achieved by neuronal control such as sympathise innervation of the heart which upreguaytes it and parasympathetic that down regulates it. Hormones can also control the stroke volume.

Question 30

What receptors are used to control the heart?

Answer 30

Chemoreceptors - pH chemicals etc
Baroreceptors- pressure
Ventral atrial stretch receptors
Unmylinated mechanoceptors

Question 31

How does the autonomic nervous system control blood vessels?

Answer 31

Sympathetic innervation of the heart releasing NA and ATP , NA acts via B1 receptors.
Adrenaline released by the adrenal medulla, which binds r0 B2 on artery’s- vasodilation and B1 on heart.
Vasoconstriction occurs in blood vessels by synaptic innervation
Parasypatic- vasodilation and slowing of heart relate M2 receptors on heart epithelium dependent on veins.

Question 32

What is the electrochemical gradient?

Answer 32

The difference between the membrane potential and the equilibrium potential

Question 33

Describe the stucture of a vein

Answer 33

Endothelial cells, line lumen with valves this is surrounded by elastin and then smooth muscle, which is surrounded by fibrous connective tissue.

Question 34

What types of blood vessels are found in the body and what are their roles?

Answer 34

1.Elastic arteries: distend significantly during systole
2.Conduit or muscular arteries, these have thick walls that prevent pinching.
3. Resistance vessels: mainly responsible for the regulation of blood pressure.
4.exchange vessels: capillaries exchange nutrients and waste from tissues.
5. Capacitance vessels: veins and venues hold most of the blood at anyone time.

Question 35

What diffrent tissues are blood vessels comprised of, what are their proportions?

Answer 35

Elastic artery: 5% endothelium, 25% smooth muscle, 40% elastic tissue, 27% collagenous tissue.
Arteriole: 10% endothelium, 60% smooth muscle,10% elastic tissue, 20% collagenous tissue.
Capillary: 95% endothelium 5% collagenous tissue.
Venule: 20% endothelium, 20% smooth muscle, 60% colelnous tissue.

Question 36

What effect does the compliance of large arteries have on the blood pressure.

Answer 36

They act like a hydronic filter smoothing the pulse flow from the heart to a steady flow through the capillaries.

Question 37

What effect does an increase in stroke volume have to pulse pressure?

Answer 37

Increases pulse pressure disproportionally.

Question 38

What effect does an increase in mean blood pressure do to the pulse pressure at the same stoke volume?

Answer 38

Same stoke volume leads to a larger pulse pressure.

Question 39

What happens to the relationship between stroke volume and pulse pressure as we age? Why is this?

Answer 39

Age increases artery stiffness, this leads to a larger increase in pulse pressure for the same stoke volume than if we were younger had had more elastic arteries.

Question 40

What constipate of blood contacts the edge of the blood vessel?

Answer 40

Plasma flows next to the endothelium (during laminar flow
) this reduces blood viscosity in small resistance vessles.

Question 41

Why do red blood cells flow in single flow through capillaries?

Answer 41

Short diffusion distance, the arrangement has very low resistance to flow so aids perfusion.

Question 42

How can we regulate local blood pressure?

Answer 42

The diameter of the arteries supplying blood to that area can be modulated, larger arteries = more flow, smaller = less