23. Electrical activity of the heart, electromechanical coupling

Question 1

What should be mentioned in this essay?

Answer 1

• Membrane potential
• Electrical activity of the heart
• Pacemaker cells
• Neural factors influencing heart
• Vagus escape
• Conduction system
• Working muscle fibers
• Action potential of working fibers
• Electrical properties of the heart
• Refractory phases of working heart muscle fibers
• Fibrillations
• Electromechanical coupling

Question 2

Membrane potential

Answer 2

Membrane potential = electrical differences measured between the outer and inner side of the membrane (sarcolemma)

-Resting membrane potential (RMP):
Electrical differences measured between the outer and inner side of the membrane in resting state − Cca. -90 mV

-Action potential (AP):
Following certain stimuli, ion channels of the membrane open and the ion exchange between the two sides lead to electrical changes called action potential

Question 3

There are 3 excitable tissues in the myocardium:

Answer 3

1. Pacemakers
   has no permanent resting membrane potential, but turns into constant depolarization (lifetime pacemaker)

2.Conductive system
provides rapid spreading of stimuli, hence providing synchronized contraction between atria and ventricles.

3.Working fibers
generate unique, elongated AP (plateau), which prevents the heart from early secondary contraction.

Question 4

Additional elements of the myocardium:

Answer 4

Additional elements:

Anulus fibrosus (non conducting)

Aschoff-Tawara node (AV node) delays the atrial signal, so the synchronous atrial contraction precedes the synchronous ventricular one.

Question 5

Pacemaker cells:

Answer 5

Pacemaker cells :
Heart muscle cells, located in the sinoatrial and atrioventricular node. Their main role is the continuous generation of the excitation.

• There is no clear resting membrane potential. During repolarization the transmembrane potential reaches -55 mV, an automatic depolarization follows.
• Round pacemaker cells: sites of the generation of the excitation.
• The elongated or slender cells conduct and probably synchronize the excitation generated in the round pacemaker cells.
• The pacemaker potential is the result of specialized ion channels of the round cells.

Question 6

Pacemaker cell picture

Answer 6

Question 7

AP is generated in sinus node from cell to cell conduction, Picture

Answer 7

Question 8

Phases of the pacemaker cells function:

Answer 8

1. MDP(maximal diastolic potential; virtual resting membrane potential)
   =slow Na+ channels opens spontaneously – slow depolarization begins
2. SDD (Spontaneous diastolic depolarization)
   =There is no resting membrane potential (RMP) − Till threshold potential
3. “overshoot”
   =much lower positive values (+5/+15 mV) than in working fibers (+25 mV)
   =Ca2+ influx and only slow Na+ channels

4.Repolarization
− K+ efflux till MDP

Question 9

AP of pacemaker and working fiber

Answer 9

• Result of Ih channel opening; depolarization occurs.
• The depolarization opens two types of calcium channels (Type-T, rianodin sensitive and type-L, DHP sensitive)
• These causes calcium to flow from the EC into the cell creating a Ca-influx.
• Depolarization continues until the threshold potential is reached: this particular segment (from the MDP to the TP(threshold ,pot.) is called spontaneous diastolic depolarization (SDD).
• There is no fast sodium channel in the membrane of the round cells. Therefore the “0” phase is determined on long- lasting Ca-channels: the development of this phase is much slower than in working fibers.
• A toxin that specifically blocks fast sodium channels, causes the disappearance of the fast upstroke proving the role of fast channels in shaping of the “0” phase.)
• The opening of potassium channels cause the efflux (out of cell) of potassium ions, repolarization begins.
• Repolarization continues until MDP is reached, activation of Ih channels starts the new cycle.

Question 10

The „Vagus Escape”

Answer 10

Under normal conditions the heart is controlled by n. vagus: − Its continuous AP discharge slows down the original activity of the heart

-Vagus escape:

− In stimulation of nervus vagus causes a strong drop in the ventricular pressure (P gets close to 0), but after a while the normal ECG and blood pressure returns,

− so the effectiveness of further stimulation of vagus disappears

− The result is a switch from nomotop to heterotop Excitation (the rhythm generator now is the AV-node and not the SA-node).

Question 11

Neural factors influencing heart rate:

(Sympathetic and Parasympathetic)

Answer 11

By stimulating the round cells of SA node:

Sympathetic effect:

1. Stimulation of β1-Rec (beta-adrenergic receptor)
   - Non specific Na+ and K+ channel open
   - MDP (max diastolic potential) shifted upwards, steepness (Steepness definition, having an almost relatively high gradient, as a hill, stairs, etc.)of SDD (spontaneous diastolic depolarization) increases, threshold is reduced.
   - Therefore heart rate (Fr) is increased.
2. The same effect can be triggered by norepinephrine (neural
   signal) and epinephrine (endocrinological signal) as well.
3. Simultaneously, parasympathetic suppression happens

(with NPY co-transmission), which increase the effect.

• Parasympathetic Effects:
  1. Acetylcholine (from vagal nerv endings) stimulate receptors on round cells.
• cAMP decreases, consequently MDP is shifted down, SDD slope decreases, threshold potential elevates, and hyperpolarization occurs
• heart rate decreases
  2. Metabotropic effect also happens (metabolic character):
• acetylcholine opens the K+ channels, resulting in further hyperpolarization and decreased frequency.

Question 12

Conduction system (Picture)

(His bundle, Tavara bundle, Purkinje fibers)

Answer 12

Question 13

Conduction system

(Small and large animals)

Answer 13

Small animals:

Subendocardial conduction = conductive fibers do not go deeply into working muscle.

Large animals:
Subepicardial conduction = deeply into ventricle

Question 14

Normal conduction data (picture)

Answer 14

Question 15

Conduction system

Answer 15

Conduction System:

1. -If the signal comes: from sinus (SA) node - Nomotop excitation ( the action of exciting or the state of being excited)
   - If the signal comes: from atrio-ventricular (AV) node = heterotop excitation

−In normal cycles, it delays the conductivity

2. Anulus Fibrosus
   − represents electric resistance – it synchronizes the atrio- ventricular cooperation

3.His bundle → Tawara bundles → Purkinje fibers
− responsible for fast conduction.

Question 16

Action potential of working fiber (picture)

Answer 16

Question 17

Electrical properties of the heart

Answer 17

• *Resting membrane potential (RMP)**
• In pacemaker cells, RMP does not exist. In diastole, spontaneous depolarization occurs, followed by an AP.

Ion flow during action potential (working fibers)
-Depolarization: voltage-gated Na+ opens. These channels are inactivated at +25mV (oveershoot)

• Rapid repolarization: short Cl- influx and K+ efflux
• Plateau: slow Ca++ influx, an slow K+ efflux. Plateau phase is shorter closer to the epicardium.
• Rapid repolatization: strong K+ (late K+ channels). Na+ and Ca++ channels are inactive
• Late hyperpolarization: At the end of AP, membrane potential sinks below the RMP (because K+ channels are inactivated slowly)

The flow of charges across the membrane is dependent on the permeability and on the electrochemical gradient.

Besides the voltage-dependent ion channels, there are other channels, which are under the control of the hormones and neurotransmitters controlling the function of the heart.

Voltage-gated channels: The so called potential (voltage)-dependent Na channels open, inactivate and close in function of the actual potential difference. These channels are responsible for the generation of the action potential.

In phase 1 of the AP, the early potassium channels.
In phase 2 the slow potassium channels.
In phase 3 the late potassium channels open. This is the reason why the potassium conductance increases until the end of the AP.

Just after the 1st phase of the AP the overshoot activates the calcium channels. Calcium ion - as a positive charge - enters the cell and therefore the repolarization is elongated.

Question 18

Plateau phase

Answer 18

It is longer close to the endocardium, and shorter closer to the epicardium

Role of plateau phase:
− is to prevent a premature generation of a new AP.

Question 19

Refractory periods (picture)

Answer 19

Question 20

Refractory phases

Answer 20

Absolute refractory phase:

• No stimulus can bring a new action potential before the end of phase 2 (plateau) in the working fiber of the heart.
• Rational: in this phase all necessary ion channels that participate in the depolarization are either in use or inactive

Relative refractory phase

• A stimulus given after the end of the plateau phase but before reaching the threshold potential, shows the strength.
• Strong stimuli can bring the formation of a new action potential. This phase is therefore named as “Relative Refractory Period”, RRP.
• Rational: some ion channels are active again (after inactive state). Therefore only stronger stimuli can cause enough strong depolarization effect
• *Supernormal phase**
• Most important period is the one between the threshold and the RMP.
• Already a slight stimulus can bring a new AP, produce a premature new contraction.
• A non-working (sick) fiber generates a small battery and stimulates the normal working fibers, when they get into their SNP. This leads to renewed premature contractions and can be fatal when it happens in the ventricle (fibrillation).

Question 21

Fibrillations

Answer 21

Atrial Fibrillation

-electric stimulation of the atrium, repeated premature contractions, the normal atrial stimulus stops. The ventricle however maintains the normal circulatory Pressure. Atrial fibrillation is not lethal, though initiates inconvenient symptoms.

• *Ventricular Fibrillation**
• In that case the normal blood Pressure can not be maintained, it may drop to 0 (heart works „empty”), normal systole and diastole disappear – it is lethal

Defibrillation

-with strong electric current – desynchronization is stopped – SA node is synchronized again, we have normal rhythm generation, so nomotop excitation is back.

Question 22

Electromechanical coupling

Connection between electric stimulus (excitation) and mechanical signal (contraction)

Answer 22

Structural unit is the DIAD

1. Action potential (AP) spreads onto the cell
2. AP reaches the T-tubules and activates the tubular L-type Ca++ channel

3.Conformation changes of L-type channels opens the T-type channels on the SR (rianodin-sensitive channels)
− A large amount of Ca gets into the sarcoplasma from SR

4. Elevating sarcoplasmatic level of Ca++ opens the Ca++- dependent Ca++ channels on the SR
5. And elevating sarcoplasmatic level of Ca++ also opens the Ca++-dependent Ca++ channels on the cell membrane.

Result: huge amount of Intra Cytoplasmic Ca++ is around the sarcomeres → contraction.

Elimination of calcium signal:
− After the contraction:

1. Na+/Ca2+ antiporter into extracellular space
2. ATP-dependent Ca2+ transporter into SR

↓

− IC Ca2+ concentration decreases, leading to relaxation

• *-Structural unit is the diad**
• T-tubules and Sarcoplasmic Retic.(SR) are in contact here.
• AP – huge Ca++-transient
• results in contraction
• After (during) contraction: ATP-dependent Ca++ pump drives back the Ca++ to the SR, plus Na+/Ca++ antiport pumps back the Ca to EC space

− Thus IC Ca++ concentration drops – results in relaxation.

Question 23

Electromechanical coupling (picture 1)

Answer 23

Question 24

Electromechanical Coupling

(Elimination of calcium signal) (picture 2)

Answer 24