Cardiac Contraction

Question 1

What stimulates the cardiac muscle contraction

Answer 1

The action potential in cardiac muscle is stimulated by the AV node.

Question 2

What is the first step of cardiac contraction

Answer 2

The first step is that voltage

gated sodium channels open causing depolarisation of the cell and giving it a positive potential.

Question 3

What happens after the cell becomes depolarised

Answer 3

This triggers the opening of voltage gated potassium channels as well as the slow opening of calcium
channels. This causes an initial repolarisation phase before a plateau phase is reached where both
calcium and potassium channels are open and oppose each other’s effects. After this phase, calcium
channels close and potassium channels fully open causing full repolarisation and slight hyperpolarisation.

Question 4

How is the resting potential restored

Answer 4

The resting potential is then restored by the sodium/potassium pump. During the plateau phase, intracellular calcium levels rise and this is the phase when cardiac muscles contract.

Question 5

What is equivalent in diastole when contraction occurs

Answer 5

The force of contraction is proportional to the amount of calcium inside the cell. In diastole, there is
around 0.1 micromoles of calcium whilst the maximum systole is 10 micromoles.

Question 6

What determines contraction of cardiac cells

Answer 6

Contraction is determined by increase in calcium levels inside the cell.

Question 7

Describe the functionality of calcium - calcium induced calcium release

Answer 7

Calcium enters the cell via
voltage gated calcium channels (VGCCs). When these channels are opened by voltage, calcium
influxes into the cell. This calcium can bind to ryanodine receptors on the sarcoplasmic reticulum and
this triggers the release of calcium from calcium stores inside. This phenomena is known as calcium
induced calcium release (CICR).

Question 8

How are the voltage gated calcium channels triggered

Answer 8

The VGCCs are triggered by an action potential depolarising t-tubules
(invaginations in the membrane of cardiac muscle).

Question 9

Describe the contraction in terms of myosin

Answer 9

The calcium in the cardiac muscle cell then binds
to troponin that causes it to displace the tropomyosin-actin complex freeing up the myosin binding
sites on actin. The myosin heads then form a cross bridge when bound to ADP and phosphate. They
then undergo a conformational change when they release ADP and phosphate causing a power
stroke. The myosin then binds to a new ATP molecule and this breaks down the cross bridges formed
between actin and myosin. The hydrolyses of the ATP to ADP cocks the myosin head back into
position and the cycle can then restart.

Question 10

What are the three regulatory subunits of troponin

Answer 10

Troponin regulates the tropomyosin conformation and it has three regulatory subunits. Troponin C
(TnC) binds calcium ions. Troponin T (TnT) binds tropomyosin and Troponin I (TnI) binds to actin
filaments.

Question 11

What causes a conformational change in tropomyosin

Answer 11

The binding of TnC to calcium causes a conformational change in tropomyosin that causes
it to expose the myosin binding sites on actin.

Question 12

What troponin types are indication of heart attack

Answer 12

TnI and TnT are released into the bloodstream during

heart attack making them good indicators of heart attack.

Question 13

How is cardiac muscle relaxation initiated

Answer 13

Cardiac muscle relaxation is initiated by action potential repolarisation down t-tubules caused by
potassium ion influx.

Question 14

What repolarisation down the t tubule cause

Answer 14

This closes VGCCs that stops calcium influx and therefore CICR as well. A
sodium/calcium exchanger expels around 30% of the calcium in the cell. The remaining 70% of
calcium in the cell is taken up into the SR by a calcium
ATPase. A small amount of calcium is taken up into the
mitochondria. The result of the reduced calcium
concentration in the cell means the cardiac muscle
relaxes as actin/myosin binding is reduced. The
chambers of the heart can now relax and fill with
blood. Calcium levels also effect the starling curve (see
curve right).

Question 15

What is used to treat acute or chronic heart failure

Answer 15

Clinical drugs that increase contractility of
the heart that are used to treat acute or
chronic heart failure mainly increase
calcium levels in cardiac muscle cells. In
general, they either increase VGCC activity
(sympathetic mimetic) or reduce calcium
extrusion (cardiac glycosides).

Question 16

What does the sympathetic mimeticus utilise

Answer 16

Sympathetic mimetics utilise the effect noradrenaline has on beta-1
receptors. This causes the phosphorylation by PKA of VGCC and increases there sensitivity to
depolarisation (see pharmacology notes).

Question 17

What does pka do

Answer 17

PKA also increases the rate at which potassium channels
fully open meaning there is a shorter action potential and quicker repolarisation. PKA also increases
the activity of SR calcium ATPase so reuptake of calcium is faster allowing for faster relaxation.

Question 18

What is the overall effect of pka drugs

Answer 18

The
overall effect of these drugs is stronger and quicker contractions (see graph on the left with
sympathetic effect in blue).

Question 19

Sympathetic mimetics are therefore beta-1 agonists.

Give examples.

Answer 19

Examples include 
dopamine and dobutamine that are used in acute heart failure.
Cardiac glycosides (e.g. digitalis or digoxin) reduce the expulsion of calcium from cardiac muscle cells.

Question 20

What is another name used for heart drugs

Answer 20

These drugs are known as inotropes and they increase the strength of contraction of the heart.

Question 21

What are other inotropic agents - and what are they used for

Answer 21

Other
inotropic agents include glucagon that acts as a GPCR that stimulates the Gs pathway that increases
cAMP and PKA activity. This drug is used for patients suffering from acute heart disease that are
taking beta-blockers (e.g. for high blood pressure).

Question 22

What is amrinone

Answer 22

Amrinone is a phosphodiesterase inhibitor (Type
III phosphodiesterase or PDE3). Phosphodiesterases convert cAMP to AMP with the result being
reduced PKA activity. Inhibiting the phosphodiesterase in the heart maintains cAMP levels that
continue to activate PKA. PKA then goes on to phosphorylate VGCCs that causes an increase in
calcium influx.