Cardiovascular control 1

Question 1

Describe the membrane potential when there is no movement of ions

Answer 1

There is no membrane potential

Question 2

Why do different cells have different shapes for their action potentials

Answer 2

Due to different currents flowing.

Question 3

Describe the potassium hypothesis

Answer 3

▪ The membrane is more permeable to potassium ions than anything else and these can diffuse down a concentration gradient, carrying positive charge with them. ▪ As they move, the incident chamber becomes increasingly positive relate to the other chamber (as other negative ions cannot move due to the barrier being impermeable to them). ▪ The electrical gradient then directly opposes the concentration gradient and eventually you get a point when the electrical gradient = the concentration gradient and equilibrium is achieved

Question 4

What is the importance of the Na+/K+ pump

Answer 4

Without it, concentration gradients would collapse, signalling mechanisms and cardiac contraction would fail.

Question 5

During the upstroke of AP, when the membrane is only permeable to sodium, will the sodium equilibrium potential be reached

Answer 5

No, due to the inactivation of the Na+ channels

Question 6

Describe the movement of K+ ions at equilibrium

Answer 6

At equilibrium, K+ ions move randomly back and forth

The driving force, the difference between the concentration and the electrical gradient, is zero at equilibrium

Question 7

Explain how we can calculate resting membrane potential

Answer 7

If the membrane is only permeable to K+ at rest (diastole) then the potential across it will equal the K+ equilibrium potential, (EK)
Equilibrium potential is calculated by solving the Nernst equation for K +

Question 8

What is the membrane potential better described by

Answer 8

In reality membrane potential is better described by the Goldman-Hodgkin-Katz equation
Takes into account the relative permeabilities of several ions simultaneously

Question 9

What controls the duration and strength of contraction of the heart

Answer 9

The duration of the action potential.

Question 10

Describe how the cardiac action potential compares with the nerve action potential

Answer 10

Compared with nerves the cardiac action potential is very long (200-300 ms vs. 2-3 ms)

Question 11

Why is the duration of the cardiac action potential important

Answer 11

Long, slow contraction is required to produce an effective pump

Question 12

Describe what is meant by absolute refractory period

Answer 12

Absolute refractory period (ARP) = time during which no action potential can be initiated regardless of stimulus intensity

Question 13

Describe what is meant by relative refractory period

Answer 13

Relative refractory period = period after ARP where an AP can be elicited but only with stimulus strength larger than normal.

Question 14

What are refractory period caused by

Answer 14

Refractory periods are caused by Na+ channel inactivation
Na+ channels recover from inactivation as the membrane repolarises
As it repolarises more, more Na+ channels are activated, hence the likelihood of generating an action potential increases (larger depolarisation from the same stimulus).

Question 15

What is meant by full recovery time

Answer 15

Full recovery time (FRT) = the time at which a normal AP can be elicited with a normal AP.

Question 16

At what membrane potential does full recovery time occur

Answer 16

Around -85mV.

Question 17

What is meant by tetany

Answer 17

Series of contractions following a series of stimuli.

Question 18

What is the importance of the long refractory period seen in cardiac muscle cells

Answer 18

In cardiac muscle, the long refractory period means it is not possible to re-excite the muscle until the process of contraction is well underway hence cardiac muscle cannot be tetanised
it also allows the heart to fill fully before the arrival of the next stimulus.

Question 19

What are the phases of the action potential in cardiac muscle

Answer 19

Phase 0 - upstroke
Phase 1- Early repolarisation
Phase 2- Plateau
Phase 3- Repolarisation
Phase 4- Resting membrane potential.

Question 20

What is the resting membrane potential determined by

Answer 20

At rest, membrane potential determined by K+. o Large membrane permeability to K+ stabilises membrane potential reducing risk to arrhythmias by requiring a large stimulus to excite the cells.

Question 21

What causes the rapid upstroke

Answer 21

Upstroke determined by large increase in membrane to Na+ permeability

Question 22

What are the two consequences of the increase in permeability to sodium ions

Answer 22

a. Large [Na+] Intracellular inactivates Na channels and thus reduces PNa quickly and this causes a brief increase in PK which gives the characteristic notch on the graph as K leaves the cell. Na channels enter absolute refractory period.
b. Large [Na+] Intracellular also increases PCa early in plateau via LTCC. Influx provides trigger for Ca2+ release from intracellular stores for contraction.

Question 23

What causes the plateau on the graph

Answer 23

2. The Ca2+ intracellular increase combined with the K+ efflux maintains the plateau of the graph.
3. Plateau ends when PCa decreases and a slow and small increase in PK occurs.

Question 24

What causes the repolarisation of the cardiac muscle

Answer 24

4. Repolarisation occurs due to inactivation of LTCC and opening of another subtype of K+ channels.

Question 25

Describe the events that take place during early repolarisation

Answer 25

Inactivation of sodium channels (no further depolarisation) and the transient outward (TO) potassium current starting.

Question 26

Describe the events that take place during the plateau phase

Answer 26

▪ Large intracellular sodium causes calcium influx which triggers CICR from intracellular stores. ▪ Potassium efflux and calcium influx stabilise the membrane potential around 0mV. ▪ Calcium influx can be blocked by dihydropyridine calcium channel antagonists (bind to LTCC, blocking the channel) such as Nifedipine, Nitrendipine and Nisoldipine.

Question 27

Describe what happens during the repolarisation phase

Answer 27

▪ Small potassium current starts to activate towards the end of the plateau which begins repolarisation. ▪ As the membrane becomes repolarised (due to efflux of potassium via normal potassium channels), the IK1 potassium channel switches back on (it turns off during depolarisation). ▪ The IK1 current is large and flows during diastole → it acts to stabilise the resting membrane potential and reduce risk of arrhythmia.

Question 28

Describe the IK1 channels

Answer 28

Large K+ current (IK1) that is inactive during the plateau starts to flow once the cells have partially repolarised IK1 is responsible for fully repolarising the cell

Question 29

Why do different parts of the heart have different action potential shapes

Answer 29

Caused by different ion currents flowing and different ion channel expression in cell membrane

Question 30

Draw action potentials for the ventricle and the sino-atrial node

Answer 30

See diagram!

Question 31

Does the SA node have a resting potential

Answer 31

No, it is always oscillating.

Question 32

Describe the intrinsic properties of the heart

Answer 32

Capable of independent spontaneous generation and coordinated propagation of electrical activity The heart can beat independently even after being separated from its nerve supply The extrinsic nerve supply coming from the autonomic nervous system serves to modify and control the intrinsic beating established by the heart

Question 33

What do the different graph shapes for the action potential in different parts of the heart produce

Answer 33

▪ These graph shapes combined create the iconic PQRST shaped wave.

Question 34

What causes the small depolarisation seen in the SA node

Answer 34

Sodium influx, different and less rapid sodium channels to that of nerves and cardiac muscle Also by T-type calcium channels which activate at more negative potentials than L-type

Question 35

What causes the upstroke in the SA node

Answer 35

There is very little sodium influx into SA node cells, instead, the upstroke is caused by Ca2+ influx. Through L-type calcium channels.

Question 36

What causes repolarisation in the SA node

Answer 36

Inactivation of L-type calcium channels, increasing permeability to potassium ions.

Question 37

Which channels are not expressed in the SA node and what is the consequence of this

Answer 37

IK1 channels Repolarisation is caused by The ITO (transient outward) current which is very small. Less stable membrane potential, due to lower membrane potential, making it easier to activate again.

Question 38

What current is present in the SA node

Answer 38

Pacemaker current (If) present

Question 39

Where else are L-type calcium channels present

Answer 39

Smooth muscle Ca2+ blockers can be used as anti-hypertensive therapy, preventing smooth muscle contraction and thus decreasing the pressure.

Question 40

What is the key to controlling the cardiovascular system

Answer 40

Controlling heart rate

Question 41

Describe the effect of sympathetic stimulation on the heart

Answer 41

With sympathetic stimulation of the heart (e.g. adrenaline), it makes the pacemaker potential (the gradual upward slope before the -40mV line) steeper This means threshold potential is reached more quickly. Heart rate increases

Question 42

Describe the effect of parasympathetic stimulation on the heart

Answer 42

With parasympathetic stimulation (e.g. ACh) there is a decrease in the gradient of pacemaker potential. Takes longer for membrane potential to meet the threshold thus reducing heart rate.

Question 43

Where are the cardio regulatory and vasomotor centres found

Answer 43

In the medulla of the brainstem.

Question 44

What does SNS innervation increase

Answer 44

``` SNS innervation increases heart rate (chronotropy) and contractility (Inotropy) ```

Question 45

Describe the SA node

Answer 45

SA node lies just below the epicardial surface at the boundary between the right atrium and the superior vena cava The specialised cells that comprise the node mark the start of the conduction pathway They spontaneously depolarise which allows the heart to generate its own rhythm (autorhythmicity)

Question 46

What are the 4 parts of the conduction system of the heart

Answer 46

Sinoatrial Node Inter-nodal Fibre Bundles. Atrioventricular Node Ventricular bundles

Question 47

What is meant by the SA node

Answer 47

Specialised cluster of autorhythmic cells

Question 48

Describe the inter-nodal fibres

Answer 48

Rapid conduction tracts to stimulate atrial myocardium | Conduct AP to AV-node at a greater velocity than ordinary atrial muscle.

Question 49

Describe the AV node

Answer 49

Specialised cells to delay wave of excitation and insulate from superior ventricular myocardium- allows atria to fully empty before the ventricles contract Produces a delay of ~100ms.

Question 50

Describe the Bundle of His and ventricular bundles

Answer 50

Bundle of his- Rapid conduction cells to transport an insulated wave of excitation Ventricular fibres- Propagate the impulse across the ventricular myocardium o Bundle of His descends from AV-node and splits into two bundle branches made of Purkinje fibres o Purkinje Fibres - conduct AP at around 6x the velocity ordinary cardiac muscle and penetrate 1/3rd distance into myocardial wall.

Question 51

Describe impulse propagation in the heart

Answer 51

Impulses are propagated between cells by the use of gap junctions (cluster at intercalated discs) which have a low resistance. The effect of depolarisation gradually decays. The propagation of the cardiac action potential is due to a combination of passive spread of current and the existence of a threshold which, once reached, causes the cell to generate its own action potential.

Question 52

Describe the gap junctions

Answer 52

Gap junctions greatly reduce membrane resistance allowing current to easily leak from one cell to a neighbouring cell. Intercellular communication and impulse conduction from one cell to the next relies on gap junctions Gap junctions form at intercalated discs Many connexons are found within the gap junction.