Sinoatrial node
The sinoatrial node is a group of cells located in the wall of the right atrium of the heart. These cells have the ability to spontaneously produce an electrical impulse, that travels through the heart via the electrical conduction system causing it to contract. In a healthy heart, the SA node continuously produces action potential, setting the rhythm of the heart and so is known as the heart's natural pacemaker. The rate of action potential production is influenced by nerves that supply it.
Structure
The sinoatrial node is a banana-shaped structure that varies in size, usually between 10-30 millimeters long, 5–7 mm wide, and 1–2 mm deep.Location
The SA node is located in the wall of the right atrium, laterally to the entrance of the superior vena cava in a region called the sinus venarum ''. It is positioned roughly between a groove called the crista terminalis located on the internal surface of the heart and the corresponding sulcus terminalis, on the external surface. These grooves run between the entrance of the superior vena cava and the inferior vena cava.Microanatomy
The cells of the SA node are spread out within a mesh of connective tissue, containing nerves, blood vessels, collagen and fat. Immediately surrounding the SA node cells are paranodal cells. These cells have structures intermediate between that of the SA node cells and the rest of the atrium. The connective tissue, along with the paranodal cells, insulate the SA node from the rest of the atrium, preventing the electrical activity of the atrial cells from affecting the SA node cells. The SA node cells are smaller and paler than the surrounding atrial cells, with the average cell being around 8 micrometers in diameter and 20-30 micrometers in length. Unlike the atrial cells, SA node cells contain fewer mitochondria, fewer myofibers, and a smaller sarcoplasmic reticulum. This means that the SA node cells are less equipped to contract compared to the atrial and ventricular cells.Action potentials pass from one cardiac cell to the next through pores known as gap junctions. These gap junctions are made of proteins called connexins. There are fewer gap junctions within the SA node and they are smaller in size. This is again important in insulating the SA node from the surrounding atrial cells.
Blood supply
The sinoatrial node receives its blood supply from the sinoatrial nodal artery. This blood supply, however, can differ hugely between individuals. For example, in most humans, this is a single artery, although in some cases there have been either 2 or 3 sinoatrial node arteries supplying the SA node. Also, the SA node artery mainly originates as a branch of the right coronary artery; however in some individuals it has arisen from the circumflex artery, which is a branch of the left coronary artery. Finally, the SA node artery commonly passes behind the superior vena cava, before reaching the SA node; however in some instances it passes in front. Despite these many differences, there doesn’t appear to be any advantage to how many sinoatrial nodal arteries an individual has, or where they originateVenous drainage
There are no large veins that drain blood away from the SA node. Instead, smaller venules drain the blood directly into the right atrium.Function
Pacemaking
The main role of a sinoatrial node cell is to initiate action potentials of the heart that can pass through cardiac muscle cells and cause contraction. An action potential is a rapid change in membrane potential, produced by the movement of charged atoms. In the absence of stimulation, non-pacemaker cells have a relatively constant membrane potential; this is known as a resting potential. This resting phase ends when an action potential reaches the cell. This produces a positive change in membrane potential, known as depolarization, which is propagated throughout the heart and initiates muscle contraction. Pacemaker cells, however, do not have a resting potential. Instead, immediately after repolarization, the membrane potential of these cells begins to depolarise again automatically, a phenomenon known as the pacemaker potential. Once the pacemaker potential reaches a set value, the threshold potential, it produces an action potential. Other cells within the heart can also initiate action potentials; however, they do so at a slower rate and therefore, if the SA node is functioning properly, its action potentials usually override those that would be produced by other tissues.Outlined below are the 3 phases of a sinoatrial node action potential. In the cardiac action potential, there are 5 phases, however pacemaker action potentials do not have an obvious phase 1 or 2.
Phase 0
This phase is also known as the pacemaker potential. Immediately following repolarization, when the membrane potential is very negative, the voltage slowly begins to increase. This is initially due to the closing of potassium channels, which reduces the flow of potassium ions out of the cell. Hyperpolarization also causes activation of hyperpolarisation-activated cyclic nucleotide–gated channels. The activation of ion channels at very negative membrane potentials is unusual, therefore the flow of sodium and some K+ through the activated HCN channel is referred to as a funny current. This funny current causes the membrane potential of the cell to gradually increase, as the positive charge is flowing into the cell. Another mechanism involved in pacemaker potential is known as the calcium clock. This refers to the spontaneous release of calcium from the sarcoplasmic reticulum into the cytoplasm, also known as calcium sparks. This increase in calcium within the cell then activates a sodium-calcium exchanger, which removes one Ca2+ from the cell, and exchanges it for 3 Na+ into the cell further increasing the membrane potential. Calcium later reenters the cell via SERCA and calcium channels located on the cell membrane. The increase in membrane potential produced by these mechanisms, activates T-type calcium channels and then L-type calcium channels. These channels allow a flow of Ca2+ into the cell, making the membrane potential even more positive.
Phase 1
This is the depolarization phase. When the membrane potential reaches the threshold potential, the cell begins to rapidly depolarise. This is mainly due to the flow of Ca2+ through L-type calcium channels, which are now fully open. During this stage, T-type calcium channels and HCN channels deactivate.
Phase 2
This phase is the repolarization phase. This occurs due to the inactivation of L-type calcium channels and the activation of potassium channels, which allows the flow of K+ out of the cell, making the membrane potential more negative.
Nerve supply
depends on the rate at which the sinoatrial node produces action potentials. At rest, heart rate is between 60 and 100 beats per minute. This is a result of the activity of two sets of nerves, one acting to slow down action potential production and the other acting to speed up action potential production.The sympathetic nerves begin in the thoracic region of the spinal cord. These nerves release a neurotransmitter called noradrenaline. This binds to a receptor on the SA node membrane, called a beta-1adrenoceptor. Binding of NA to this receptor activates a G-protein which initiates a series of reactions that results in the production of a molecule called cyclic adenosinemonophosphate. This cAMP binds to the HCN channel. Binding of cAMP to the HCN, increases the flow of Na+ and K+ into the cell, speeding up the pacemaker potential, so producing action potentials at a quicker rate, and increasing heart rate. An increase in heart rate is known as positive chronotropy.
The parasympathetic nerves supplying the SA node originate in the brain. These nerves release a neurotransmitter called acetylcholine. ACh binds to a receptor called an M2 muscarinic receptor, located on the SA node membrane. Activation of this M2 receptor, then activates a protein called a G-protein. Activation of this G-protein, blocks the cAMP pathway, reducing its effects, therefore inhibiting sympathetic activity and slowing action potential production. As well as this, the G-protein also activates a potassium channel, which allows K+ to flow out of the cell, making the membrane potential more negative and slowing the pacemaker potential, therefore decreasing the rate of action potential production and therefore decreasing heart rate. A decrease in heart rate is known as negative chronotropy.
The first cell to produce the action potential in the SA node isn’t always the same, this is known as pacemaker shift. In certain species of animals, for example, in dogs, a superior shift usually produces an increased heart rate whereas an inferior shift produces a decreased heart rate.
Clinical significance
Sinus node dysfunction describes an irregular heartbeat caused by faulty electrical signals of the heart. When the heart's sinoatrial node is defective, the heart’s rhythms become abnormal – typically too slow or exhibiting pauses in its function or a combination, and very rarely faster than normal.Blockage of the arterial blood supply to the SA node can therefore cause ischaemia and cell death in the SA node. This can disrupt the electrical pacemaker function of the SA node, and can result in sick sinus syndrome.
If the SA node does not function, or the impulse generated in the SA node is blocked before it travels down the electrical conduction system, a group of cells further down the heart will become its pacemaker.