Thành viên:Naazulene/Tế bào tạo nhịp

Trang này viết về the natural pacemaker in the heart. Đối với the medical device that simulates the function, xem Artificial cardiac pacemaker.

Image showing the cardiac pacemaker or SA node, the primary pacemaker within the electrical conduction system of the heart

Tế bào tạo nhịp hay tế bào nút là tế bào tạo tín hiệu co bóp cho trái tim. Nó là một trong hai loại tế bào cơ ở tim (loại còn lại là tế bào co bóp) xuất hiện chủ yếu ở nút xoang nhĩ (nút SA) và ít hơn ở nút nhĩ thất. Các tế bào này được biệt hóa để không còn có cấu trúc sarcomere.

Sự co bóp cơ tim ở tất cả động vật đều xuất phát từ xung động điện. Ở cơ thể khỏe mạnh, các trung tâm tạo nhịp ở nút xoang nhĩ thực hiện chức năng này. Nếu nút xoang nhĩ hay hệ thống dẫn truyền điện của trái tim bị hư hại, trung tâm tạo nhịp ở nút nhĩ thất có thể đứng ra thay thế. Bệnh nhân rối loạn nhịp có thể được cấy máy tạo nhịp tim nhân tạo để thay thế các cơ chế tạo nhịp và dẫn truyền bị hư hại.

Cấu trúc

Tế bào tạo nhịp được biệt hóa từ tế bào co bóp (tức tế bào cơ tim) để thực hiện chức năng đặt thù của nó. Đặc điểm cấu trúc nổi bật nhất là nó không có cấu trúc sarcomere; sarcomere là các sợi vân thực hiện chức năng co bóp trong tế bào cơ.

Để thực hiện chức năng tạo nhịp, tế bào tạo nhịp có ba kênh ion quan trọng: kênh Ca²⁺, kênh K⁺ và kênh cười (kênh Na⁺ chậm).

Control

Schematic representation of the sinoatrial node and the atrioventricular bundle of His. The location of the SA node is shown in blue. The bundle, represented in red, originates near the orifice of the coronary sinus, undergoes slight enlargement to form the AV node. The AV node tapers down into the bundle of His, which passes into the ventricular septum and divides into two bundle branches, the left and right bundles. The ultimate distribution cannot be completely shown in this diagram.

Primary pacemaker

The sinoatrial node (SA node) is the primary pacemaker of the heart. It is a region of cardiac muscle on the wall of the upper right atrium near to the superior vena cava entrance. The cells that make up the SA node are specialized cardiomyocytes known as pacemaker cells that can spontaneously generate cardiac action potentials. These signals are propagated through the heart's electrical conduction system. Only one percent of the heart muscle cells are conductive, the rest of the cardiomyocytes are contractile.

The pacemaker cells are connected to neighboring contractile cells via gap junctions, which enable them to locally depolarize adjacent cells. Gap junctions allow the passage of positive cations from the depolarization of the pacemaker cell to adjacent contractile cells. This starts the depolarization and eventual action potential in contractile cells. Having cardiomyocytes connected via gap junctions allow all contractile cells of the heart to act in a coordinated fashion and contract as a unit. All the while being in sync with the pacemaker cells; this is the property that allows the pacemaker cells to control contraction in all other cardiomyocytes.

Cells in the SA node spontaneously depolarize, ultimately resulting in contraction, approximately 100 times per minute. This native rate is constantly modified by the activity of sympathetic and parasympathetic nerve fibers via the autonomic nervous system, so that the average resting heart rate in adult humans is about 70 beats per minute.

Secondary (AV junction and Bundle of His)

Impulses from the sinus node reach the atrioventricular node which acts as the secondary pacemaker. The cells of the AV node normally discharge at about 40-60 beats per minute, and are called the secondary pacemaker.

Further down the electrical conducting system of the heart is the Bundle of His. The left and right bundle branches, and the Purkinje fibers, will also produce a spontaneous action potential at a rate of 30-40 beats per minute, so if the SA and AV node both fail to function, these cells can become pacemakers. These cells will be initiating action potentials and contraction at a much lower rate than the primary or secondary pacemaker cells.

The SA node controls the rate of contraction for the entire heart muscle because its cells have the quickest rate of spontaneous depolarization, thus they initiate action potentials the quickest. The action potential generated by the SA node passes down the electrical conduction system of the heart, and depolarizes the other potential pacemaker cells (AV node) to initiate action potentials before these other cells have had a chance to generate their own spontaneous action potential, thus they contract and propagate electrical impulses to the pace set by the cells of the SA node. This is the normal conduction of electrical activity in the heart.

Generation of action potentials

There are 3 main stages in the generation of an action potential in a pacemaker cell. Since the stages are analogous to contraction of cardiac muscle cells, they have the same naming system. This can lead to some confusion. There is no phase 1 or 2, just phases 0, 3, and 4.

Phase 4 - Pacemaker potential

The key to the rhythmic firing of pacemaker cells is that, unlike other neurons in the body, these cells will slowly depolarize by themselves and do not need any outside innervation from the autonomic nervous system to fire action potentials.

In all other cells, the resting potential (-60mV to -70mV) is caused by a continuous outflow or "leak" of potassium ions through ion channel proteins in the membrane that surrounds the cells. However, in pacemaker cells, this potassium permeability (efflux) decreases as time goes on, causing a slow depolarization. In addition, there is a slow, continuous inward flow of sodium, called the "funny" or pacemaker current. These two relative ion concentration changes slowly depolarize (make more positive) the inside membrane potential (voltage) of the cell, giving these cells their pacemaker potential. When the membrane potential gets depolarized to about -40mV it has reached threshold (cells enter phase 0), allowing an action potential to be generated.

Phase 0 - Upstroke

Though much faster than the depolarization of phase 4, the upstroke in a pacemaker cell is slow compared to that in an axon.

The SA and AV node do not have fast sodium channels like neurons, and the depolarization is mainly caused by a slow influx of calcium ions. (The funny current also increases). Calcium enters the cell via voltage-sensitive calcium channels that open when the threshold is reached. This calcium influx produces the rising phase of the action potential, which results in the reversal of membrane potential to a peak of about +10mV. It is important to note that intracellular calcium causes muscular contraction in contractile cells, and is the effector ion. In heart pacemaker cells, phase 0 depends on the activation of L-type calcium channels instead of the activation of voltage-gated fast sodium channels, which are responsible for initiating action potentials in contractile (non-pacemaker) cells. For this reason, the pacemaker action potential rising phase slope is more gradual than that of the contractile cell (image 2).

Phase 3 - Repolarization

The reversal of membrane potential triggers the opening of potassium leak channels, resulting in the rapid loss of potassium ions from the inside of the cell, causing repolarization (V_m gets more negative). The calcium channels are also inactivated soon after they open. In addition, as sodium channels become inactivated, sodium permeability into the cell is decreased. These ion concentration changes slowly repolarize the cell to resting membrane potential (-60mV). Another important note at this phase is that ionic pumps restore ion concentrations to pre-action potential status. The sodium-calcium exchanger ionic pump works to pump calcium out of the intracellular space, thus effectively relaxing the cell. The sodium/potassium pump restores ion concentrations of sodium and potassium ions by pumping sodium out of the cell and pumping (exchanging) potassium into the cell. Restoring these ion concentrations is vital because it enables the cell to reset itself and enables it to repeat the process of spontaneous depolarization leading to activation of an action potential.

Clinical significance

Damage to the SA node

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. This center is typically represented by cells inside the atrioventricular node (AV node), which is an area between the atria and ventricles, within the atrial septum. If the AV node also fails, Purkinje fibers are occasionally capable of acting as the default or "escape" pacemaker.

Ectopic pacemaker

Illustration depicting an ectopic focus

An ectopic pacemaker also known as an ectopic focus or ectopic foci, is an excitable group of cells that causes a premature heart beat outside the normally functioning SA node of the heart. It is thus a cardiac pacemaker that is ectopic, producing an ectopic beat. If chronic this can result in arhythmias such as tachycardia, bradycardia, or ventricular fibrillation. An artificial pacemaker may be used to counter this.

Artificial pacemakers

Bài chi tiết: Artificial cardiac pacemaker

An artificial cardiac pacemaker (or artificial pacemaker, so as not to be confused with the natural cardiac pacemaker) or just pacemaker is an implanted medical device that generates electrical impulses delivered by electrodes to the chambers of the heart either the upper atria, or lower ventricles to cause the targeted chambers to contract and pump blood. By doing so, the artificial pacemaker takes over from the primary SA node pacemaker to regulate the function of the heart's electrical conduction system.