#5889 - Cardiac Function - Cardiorespiratory system

Cardiac Function

The myocardium

1. Cardiac muscle

Cardiac muscle is similar to skeletal muscle as it is striated and Ca²⁺ activated. It differs from skeletal muscle in a number of ways …

• Not a true (anatomical) syncytium.

• Nuclei are centrally located.

• More mitochondria and glycogen.

• Much richer vascularisation.

In regions where the cell membranes are folded and in close contact, the muscle cells are attached to each other end to end. These contact regions are called intercalated disks and contain numerous gap junctions. This allows action potentials to be propagated cell to cell. However, the annulus fibrosis (the fibrous tissue which separates the atria from the ventricles) blocks conduction of action potentials directly from atrial muscle to the ventricular muscle.

There are two types of cardiac muscle cells – contractile cells and autorhythmic cells.

Most of the cardiac muscle cells are contractile ones. As with skeletal muscle cells, cardiac contractile cells have a stable resting membrane potential and must be stimulated for the membrane potential to reach threshold value. However, skeletal muscle cells are stimulated by a chemical synapse, whereas cardiac contractile cells are stimulated by depolarising currents that enter through gap junctions.

Autorhythmic cardiac cells generate action potentials spontaneously by undergoing slow depolarisation until threshold potential is reached. They are concentrated in certain regions of the heart. This spontaneous depolarisation occurs most rapidly in a cluster of cells known as the SA node. When an action potential is generated in the SA node, it spreads through the myocardium and elicits contraction. The spontaneous depolarisations of other autorhythmical cells are inconsequential in normal conditions, as they are often stimulated by action potentials from the SA node before they can reach threshold potential themselves.

2. Cardiac action potentials

There are two type of cardiac action potentials …

• Non-pacemaker action potentials – also called fast response action potentials because of their rapid depolarisation. Found throughout the heart except at pacemaker cell regions.

• Pacemaker action potentials – also called slow response action potentials because of their slower rate of depolarisation. These are found in the SA and AV nodes of the heart.

Cardiac action potentials differ from action potentials found in neural and skeletal muscle tissue.

One difference is the duration of the action potentials. In skeletal muscle, action potentials last 2-5ms, whereas cardiac action potentials last 200-400ms.

Another difference is the role of calcium ions in depolarisation. In neurones and skeletal muscle cells, the depolarisation phase of the action potential is caused by opening of sodium channels. This is also true in non-pacemaker cardiac cells. However, in cardiac pacemaker cells, calcium ions are involved in the initial depolarisation phase of the action potential. The Ca2+ currents are much slower than Na+ currents. In non-pacemaker cells, calcium influx prolongs the duration of the action potential and produces a characteristic plateau phase.

SA nodal action potentials are divided into three phases …

• Phase 4 – spontaneous depolarisation of the membrane that triggers the action potential.

• Phase 0 – depolarisation phase of the action potential.

• Phase 3 – repolarisation of the membrane.

When the membrane potential is around -60mV, Na+ ion channels open. This allows slow, inward conduction of depolarising Na+ currents. This causes spontaneous depolarisation, initiating phase 4. When the membrane is around -50mV, transient or T-type Ca2+ channels open. This causes further depolarisation of the cell. At about -40mV, a second type of Ca2+ channel opens – the long-lasting or L-type Ca2+ channels. This causes further depolarisation until action potential threshold is reached. During phase 4, there is a decrease in the outward movement of K+ as these channels close. This also contributes to depolarisation.

Phase 0 is caused by increased Ca2+ conductance. Na+ channels and T-type Ca2+ channels close at this point. As movement of Ca2+ into the cell through L-type Ca2+ channels is slow, the rate of depolarisation is slower than found in other cardiac cells (such as the Purkinje fibre cells).

Phase 3 occurs as K+ channels reopen (increasing outward movement of K+) and L-type Ca2+ channels close (decreasing inward movement of Ca2+).

Action potentials in the SA node are very similar to those in the AV node.

3. The conduction system

The autorhythmic cells collectively form a specialised system for conducting action potentials through the myocardium. This system allows action potentials to be conducted more rapidly than in electrically coupled contractile muscle cells. This allows almost simultaneous contraction of the entire ventricular muscle. The specialised conduction system is poorly developed in the atria, and action potentials spread much more slowly through atrial muscle.

It also causes a delay in conduction of the impulse from the atria to the ventricles. This is possible due to the annulus fibrosis, and allows ventricular filling.

An action potential is first generated in the SA node. This spreads slowly throughout the atria by cell to cell conduction. As the wave of depolarisation spreads, the cardiomyocytes contract by a process termed excitation-contraction coupling.

The wave of depolarisation then reaches the AV node. The AV node is a collection of modified cells located close to the annulus fibrosis. It slows the rate of conduction considerably, which allows complete atrial systole prior to ventricular depolarisation.

Impulses enter the base of the ventricles at the Bundle of His, and follow the right and left bundle brnaches along the interventricular septum. These specialised fibres allow rapid conduction. At the apex of the heart, the branches divide into an extensive system of Purkinje fibres that allow even more rapid conduction throughout the ventricles. This results in rapid depolarisation of ventricular cardiomyocytes throughout both ventricles.

4. Regulation of conduction

The conduction of electrical impulses through the heart is influenced by the ANS. This is particularly apparent at the AV node. Sympathetic stimulation increases conduction velocity (positive dromotropy) at the AV node by increasing the rate of depolarisation. This reduces the delay of conduction through the AV node. This would be seen as a decrease in the P-Q interval on the ECG.

Sympathetic nerves influence the AV node by releasing the neurotransmitter norepinephrine. This binds to beta-adrenoceptors, leading to an increase in intracellular cAMP.

Parasympathetic activation decreases conduction velocity (negative dromotropy) at the AV node. This is achieved through release of the neurotransmitter acetylcholine, which binds to cardiac muscarinic receptors and decreases intracellular cAMP.

5. Regulation of heart rate

Heart rate is regulated by the ANS. It receives sympathetic innervation from nerves from the region of T2-T4 via the mid-cervical and cervicothoracic ganglia. This supplies the SA node and entire myocardium.

The heart receives parasympathetic innervation from the vagus nerve. This supplies the SA node and atria only.

Sympathetic nerve fibres release norepinephrine at the SA node, which increases heart rate by increasing the rate of drift of the pacemaker cells to threshold potential.

Parasympathetic nerve fibres release acetylcholine at the SA node, which decreases heart rate by decreasing the rate of drift to the threshold.

6. Adrenergic and cholinergic receptors in the heart

Several types of receptors exist within the heart.

Sympathetic adrenergic fibres innervate the SA and AV nodes, conduction pathways and myocytes in the heart. These nerves release the neurotransmitter norepinephrine.

Adrenergic receptors (or adrenoceptors) are receptors that bind adrenergic agonists such as norepinephrine, and the circulation hormone epinephrine. Adrenoceptors in the heart include …

• ß1 adrenoceptors. When activated by a ß1 agonist, such as norepinephrine, heart rate is increased (positive chronotropy), conduction veolicty is increased (positive dromotropy), contractility is increased (positive inotropy) and the rate of myocyte relaxation is increased (positive lusitropy).

• ß2 adrenoceptors. When stimulated by a ß2 agonist, they produce similar effects to ß1 adrenoceptors.

• Α1 adrenoceptors. These are found on myocytes and when stimulated produce small increases in inotropy.

The heart is also innervated by parasympathetic cholinergic nerves derived from the vagus nerve. These nerve fibres release the neurotransmitter acetylcholine, which binds to muscarinic receptors in the cardiac muscle, especially at the SA and AV nodes. Specifically, acetycholine binds to M2 muscarinic receptors. This produces negative chronotropy and dromotropy in the heart, and negative inotropy and lusitropy in the atria.

The autonomic nerve terminals also possess adrenergic and cholinergic receptors (prejunctional receptors) that function to regulate release of norepinephrine. Prejunctional α2 adrenoceptors inhibit norepinephrine release, whilst prejunctional ß2 adrenoceptors facilitate norepinephrine release. Prejunctional M2 receptors inhibit norepinephrine release. This is one way that parasympathetic stimulation can override sympathetic stimulation in the heart.

7. Cardiac cycle

A single cardiac cycle can be divided into two basic phases – diastole and systole.

Diastole is the period of time when the ventricles are...