Cardiac muscle

Question 1

What are the cell types in the heart

Answer 1

Fibroblasts
Neurons
Smooth muscle around coronary vessels
Myocytes

Question 2

What cell accounts for the largest volume of the heart

Answer 2

Myocytes

Question 3

Describe the cardiac myocytes (appearance, size, conduction, metabolism)

Answer 3

Striated
Less than 2 micrometres thick and about 100 micrometers long
Electrically connected to other myocytes at intercalated discs via gap junctions
Mainly oxidative in metabolism (oxidative phosphorylation in the mitochondria)

Question 4

Describe the sarcolemma

Answer 4

The myocyte cell membrane
Continuous with the T-tubules
Contains ion channels, pumps, and transporters
Outer surface of glycoclyx

Question 5

What are the constituents of the glycocalyx

Answer 5

acidic mucopolysaccharides, rich in silica acid residues

Question 6

Describe the t-tubules including main ion channel type

Answer 6

Invaginations of the sarcolemma

Rich in L-type Ca2+ channels (DHPRS)

Question 7

Describe caveolae

Answer 7

Small invaginations of the sarcolemma

Preferential location of scaffolding protein caveolin-3 and signalling molecules e.g. NO, and protein kinase.

Question 8

Describe intercalated discs

Answer 8

The region where myocytes join end to end

Include gap junctions, intermediate junctions and desmosomes

Question 9

Describe the sarcoplasmic reticulum, including two channels

Answer 9

Intracellular membrane-bounded compartment
Internal Ca2+ store
Junctional couplings with the t-tubules and sarcolemma (wraps around half the t-tubule forming diads)
Junctional SR contains ryanodine receptors (RyRs)
SERCA (SR Ca2+-ATPase) channels responsible for re-uptake of Ca2+ into the SR

Question 10

What is calsequestrin and where is it found

Answer 10

In the SR, a Ca2+ buffer. Binds 35-40 Ca2+ per one calsequestrin molecule. Once signalled by RyR receptors calsequestrin unbinds Ca2+ for its release.

Question 11

Why are L-type Ca2+ channels also called Dihydropyridine channels

Answer 11

Because they bind to the class of drugs known as dyhydropyridine’s which are Ca2+ channel blockers (slow HR).

Question 12

Describe L-type channels

Answer 12

In the sarcolemma (T-tubule)
Voltage sensitive
Responsible for the plateau phase of the AP
Inhibited by SR Ca2+ release
Opened when membrane potential reaches -40mV (following opening of Na+ channels)
Inhibited by dihydropyridine and low Cytosolic Ca2+

Question 13

Describe SERCA channels

Answer 13

Sarcoplasmic Reticulum Ca2+ ATP pumps.

Takes Ca2+ back into the SR. 2 Ca2+ for 1 ATP.

Question 14

Role of phospholambin

Answer 14

Inhibits/slows the uptake of Ca2+ by the SERCA channels. During increased cytosolic Ca2+ (exercise) phospholambin activity reduced so SR uptakes Ca2+ much faster.

Question 15

Describe the number of cardiac motor units that contract in unison

Answer 15

Every myocyte contracts in unison

Question 16

What is resting cardiac output

Answer 16

CO=SVHR CO=70mls70bpm = 4900ml or around 5 litres a minute

Question 17

What are the mechanisms for increasing heart contractile force

Answer 17

Increase rate of automaticity
Increase the dimensions of the ventricles (stretch)
Use of NT to alter rate and Ca2+ handling
Use inotropic drugs

Question 18

What are the two main ways to increase the force of cardiac muscle contraction at a cellular level?

Answer 18

Increase the Ca2+ transient

Altering myofilament Ca2+ sensitivity

Question 19

What are the factors that effect Ca2+ sensitivity of myocytes

Answer 19

Decreases:
Acidosis
Catecholamines
Inorganic phosphate
Increases:
Increased sarcomere length
Caffeine
Decreased intracellular ATP

Question 20

What sarcomere length produces maximal force (force length relationship) and why

Answer 20

2-2.2 micrometres
Increased length reduces the number of crops bridge formations
Decreased length causes cross bridge interference

Question 21

Describe the Ca2+ transient

Answer 21

Occurs when voltage gated Na+ channels are opened due to depolarisation from an AP, opening of Na+ channels further depolarises the sarcolemma and voltage gated Ca2+ channels (L-type dihydropyridine) are opened causing small influx of Ca2+. The influx acts on rynanadine RyR channels (Ca2+ dependent Ca2+ release). Until Ca2+ is removed this is the transient

Question 22

What are the mechanisms for removing Ca2+ from the cytosol

Answer 22

Ca2+ can be removed from the cytoplasm through extrusion across the sarcolemma and sequestration into the SR.
SERCA SR Ca2+ ATPase -re uptake of Ca2+ into the SR.
Sarcolemma Ca2+ pump; 1 Ca2+ for 1 ATP
Na+/Ca2+ exchanger 3 Na+ for 1 Ca2+.

Question 23

Describe the Frank-Starling law of the heart

Answer 23

Increase in end diastolic volume results in increased contractile force due to stretching of the ventricles. Increased CO

Question 24

Why is there an increase in Ca2+ transient with increased HR

Answer 24

Less time for Ca2+ extrusion, decrease in overall membrane potential inhibits the Na+/Ca2+ exchanger leading to increased intracellular Ca2+.

Question 25

Describe modulation of contractile force by NT

Answer 25

Parasympathetic (vagal) stimulation decreases SA node firing and hence force.
Sympathetic stimulation increases SA node firing, Ca2+ transient, decreases the sensitivity of troponin for Ca2+.

Question 26

Describe effects of B-adrenergic stimulation

Answer 26

Beta adrenergic receptors widely distributed throughout the heart. The act via adenyl cyclase which increases cAMP dependent protein kinase (PKA) which phosphorylates key proteins:
SL Ca2+ channels (increased intracellular Ca2+)
Phospholambin (increased SR Ca2+ pump)
Modified RyR channels

Question 27

Describe the action of carditonic steroids

Answer 27

E.g. digoxin, increases intracellular Na+ by inhibiting Na+ pump, Ca2+ extrusion is reduced due to reduction in Na+/Ca2+ exchanger