Electrophysiology of cardiac muscle

lecture 5

How does electrical excitation propagate through cardiac muscle?

cardiac cells form an electrical syncytium

electrical signal propagates through gap junctions

structure of cardiac myocytes in the SAN

fewer myofibres and mitochondria

smaller sarcoplasmic reticulum compared to atrial or ventricular cardiac myocytes

primary function generation and conduction of a pacemaker potential

Why is conduction through the AVN slower than the SAN?

AVN surrounded by a fibrous AV ring

Why is the conduction delay between the SAN and AVN important?

ensures sequence of atrial and ventricular contractions is well time

Where does the electrical signal propagate after the AVN?

bundle of His and Purkinje fibres

propagation fast because their main function is to activate contraction in the ventricle

purkinjie fibres split into 2 branches into the 2 ventricle walls

ventricles contract from the apex to the base

Why do ventricles contract from the apex to the base?

ensures max blood leaves the ventricles purely through the mechanical squeezing and pressure gradient.

What happens with damage to the SA node?

cells in the AVN and Purkinje fibres can also function as pacemakers

intrinsic pacemaker rate is slower than the SAN

fastest pace and therefore normal heart rate determined by the SAN

What is phase 0 of action potential generation in cardiac myocytes?

rapid depolarisation phase

driven by voltage-gated Na⁺ activation and slow opening of Ca²⁺ channels

more or less fast depending on the type of the cell

What is phase 1 of action potential generation in cardiac myocytes?

the initial brief rapid repolarisation

driven by opening of K⁺ channels

Na⁺ channels close to inactive state

What is phase 2 of action potential generation in cardiac myocytes?

the plateau

Ca²⁺ influx balances K⁺ efflux

Ca²⁺ channels are L-type voltage-gated channels (dihydropyridine receptors)

What is phase 3 of action potential generation in cardiac myocytes?

terminal repolarisation

delayed activation of different K⁺ channels

restores the membrane potential to the resting level

What is phase 4 of action potential generation in cardiac myocytes?

electrical diastole

returns to resting potential

heart waiting for another electrical trigger to restart the cycle

What is a consequence of this prolonged action potential?

results in long refractory period

prevents summation and tetanus from occuring

How is the SAN action potential different?

does not display rapid phase 1 depolarisation

plateau phase not very prominent

SAN cells do not have a true resting potential - membrane potential always changing

do not depolarise as much as other muscle cells

funny current

spontaneous slow increase in current during phase 4 depolarisation in SAN cells

due to non-specific cation channel (HCN channel)

HCN channel has mixed permeability for both Na⁺ and K⁺

called funny because HCN channel opens on hyperpolarisation, not depolarisation

When does the HCN channel open?

end of phase 3 depolarisation

leads to an inwards cation current

drives slow membrane depolarisation in phase 4

What does the slope of the phase 4 slow depolarisation determine?

heart rate

When potential reaches threshold (~40mV) in SAN?

Ca²⁺ channels open

rapid depolarisation but still slower than in ventricles as no Na⁺

at peak Ca²⁺ channels close & K⁺ open leading to repolarisation

effect of noradrenaline and adrenaline on funny current

increase funny current

reduce phase 3 depolarisation

increased heart rate

shorter but higher plateau in ventricular cells

stronger contraction

Calcium induced calcium release

ryanodine receptors activated through the extracellular Ca²⁺ that enters through dihydropyridine receptors

Consequences of calcium induced calcium release

1. risk of calcium overload therefore a regulatory mechanism needed to balance Ca²⁺ levels with each action potential

2. extracellular Ca²⁺ influences how much tension is being produced

How is Ca²⁺ concentration regulated during CICR?

high activity of Na⁺/Ca²⁺ exchanger in the sarcolemma

re-sequestered in SR between action potentials, controlled by SERCA pump

SERCA pump inhibition and stimulation

inhibited: Phospholamban (PLN), relieved upon phosphorylation of PLN

stimulation: adrenaline. PKA acts downstream of adrenaline & phosphorylates PLN. During fight-or-flight response, adrenaline leads to activation of SERCA pump