Electrical activation of the heart: cellular aspects

Question 1

Heart muscle

Answer 1

Atrial and ventricular muscle
Excitatory and conductive muscle fibres
Important differences compared to skeletal muscle

Question 2

Functions

Answer 2

Muscular contraction
Electrical conduction

Question 3

Resting membrane potential- membrane of heart muscle cell

Answer 3

Normally only permeable to K+
Potential determined only by ions that can cross membrane

Question 4

Resting membrane potential- negative membrane potential

Answer 4

K+ ions diffuse outwards (high to low concentration)
Anions cannot follow
Excess of anions inside the cell
Generates negative potential inside the cell

Question 5

Myocyte membrane pumps

Answer 5

K+ pumped IN to cells
Na+ and Ca2+ pumped OUT of cells
Against their electrical and concentration gradients
Therefore requires active transport (Na+-K+ pump)
Requires ATP for energy

Question 6

Cardiac action potential

Answer 6

slide 16-21

Phase 4- Resting potential
maintained by Na+/K+/ATP pump
and the Na+/K+ leak channels opening, greater loss of K+ ions out than Na+ in so -90mV

Phase 0- Depolarisation
Voltage gated Na+ channels open, influx of Na+ so increases to +20mV

Phase 1- Initial repolarization
Na+ channels close and Transient K+ channels open, for short amount of time K+ move out so small repolarization

Phase 2- Plateau
Slow Ca+ channels open. Ca2+ flow into the cell. The number of Ca2+ channels is proportional to the number of K+ channels so almost same number of Ca2+ ions moving into cells as the K+ ions moving out so reach plateau
During this plateau, the cardiomyocytes contract (excitation- contraction coupling)
Between phase 2 and 3 the relaxation of myocytes takes place as Ca2+ channels must still stay open to allow the Ca2+ to leave the cell

Phase 3- Repolarization
The slow Ca2+ channels close and rectifying K+ channels open, causing the K+ to move out
Phase 4 reached again

Question 7

What is the point of all the electrical activity?

Answer 7

Calcium

Contraction of the heart muscle requires (appropriately-timed) delivery of Ca2+ ions to the cytoplasm
“Excitation-contraction coupling”

Question 8

Extractiom contraction coupling

Answer 8

Step 1: Calcium influx through surface ion channels

Step 2: Amplification of [Ca2+]i with NaCa

Step 3: Calcium-induced calcium release

Question 9

Troponin-Tropomyosin-Actin Complex

Answer 9

Calcium binds to troponin
Conformational change in tropomyosin reveals myosin binding sites
Myosin head cross-links with actin
Myosin head pivots causing muscle contraction

Question 10

Cardiac muscle compared to skeletal muscles

Answer 10

Contraction of cardiac muscle lasts longer than skeletal muscle

Up to 15 times longer duration

Due to slow calcium channels

Decreased permeability of membrane to potassium after action potential

Question 11

Sino- Atrial Node

Answer 11

Upsloping Phase 4
Less rapid phase 0
No discernable phase 1 / 2

If – Funny current
ICa,T – Transient Calcium current
ICa,L – Long-lasting calcium current
Gradual depolarization until a threshold ~-35mV, then rapid depolarization via Ca2+ influx

Question 12

SAN- what affects it

Answer 12

Sinus node potential drifts towards threshold
The steeper the drift, the faster the pacemaker
Phase 4 slope affected by:
Autonomic tone
Drugs
Hypoxia
Electrolytes
Age

Question 13

Automatic control- sympathetic stimulation

Answer 13

Increases heart rate (positively chronotropic)
Increases force of contraction (positively inotropic)
Increases cardiac output

Question 14

Parasympathetic stimulation

Answer 14

Decreases heart rate (negatively chronotropic)
Decreases force of contraction (negatively inotropic)
Decreases cardiac output

Question 15

Sympathetic stimulation

Answer 15

Controlled by:
Adrenaline and noradrenaline + type 1 beta adrenoreceptors
Increases adenylyl cyclase  increases cAMP

Increased sympathetic stimulation
-Increases heart rate (up to 180-250 bpm)
-Increases force of contraction
-Large increase in cardiac output (by up to 200%)

Decreased sympathetic stimulation
-Decreases heart rate and force of contraction
-Decreases cardiac output (by up to 30%)

Question 16

Parasympathetic stimulation

Answer 16

Controlled by:
Acetylcholine
M2 receptors – inhibit adenyl cyclase  reduced cAMP

Increased parasympathetic stimulation
-Decreased heart rate (temporary pause or as low as 30-40 bpm)
-Decreased force of contraction
-Decreased cardiac output (by up to 50%)

Decreased parasympathetic stimulation
-Increased heart rate

Question 17

AV Node

Answer 17

Transmits cardiac impulse between atria and ventricles
Delays impulse
Allows atria to empty blood into ventricles
Fewer gap junctions
AV fibres are smaller than atrial fibres
Limits dangerous tachycardias

Question 18

Conduction in the heart

Answer 18

Velocity of conduction
Faster in specialised fibres
Atrial and ventricular muscle fibres: 0.3 to 0.5 m/s
Purkinje Fibers: 4m/s

Question 19

His-purkinje system

Answer 19

AV node  ventricles
Rapid conduction
To allow coordinated ventricular contraction
Very large fibres
High permeability at gap junctions

Question 20

Automaticity

Answer 20

Spontaneous discharge rate of heart muscle cells decreases down the heart
SAN (usually) fastest
Ventricular myocardium slowest

Question 21

Refractory Period

Answer 21

Heart muscle
Refractory to further stimulation during the action potential
Fast Na+ +/- slow Ca2+ channels closed (inactivating gates)
Normal refractory period of ventricle approx 0.25s
Less for atria than for ventricles
Prevents excessively frequent contraction
Allows adequate time for heart to fill

Question 22

After absolute refractory period
(Relative refractory period)

Answer 22

Some Na+ channels still inactivated
K+ channels still open
Only strong stimuli can cause action potentials
Affected by heart rate

Question 23

Clinical relevance 1- Extracellular potassium rises (as occurs in certain disease states)

Answer 23

Myocytes becomes less polarized (because Nernst)
 Less polarized myocytes are more easily activated / excitable
 Tachyarrhythmia