Pacemaker potential
Encyclopedia
In the pacemaking cells of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

 (e.g., the sinoatrial node
Sinoatrial node
The sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...

), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane (the membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

) that occurs between the end of one action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

 and the beginning of the next action potential. This increase in membrane potential is what causes the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

, which typically maintains a resting membrane potential of -70 mV, to reach the threshold potential
Threshold potential
The threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential.It often can be between −40 and -55 mV, but it can vary based upon several factors...

 and consequently fire the next action potential; thus, the pacemaker potential is what drives the self-generated rhythmic firing (automaticity) of pacemaker cells, and the rate of change (i.e., the slope) of the pacemaker potential is what determines the timing of the next action potential and thus the intrinsic firing rate of the cell. In a healthy sinoatrial node (SAN, a complex tissue within the right atrium containing pacemaker cells that normally determine the intrinsic firing rate for the entire heart), the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats (diastole
Diastole
Diastole is the period of time when the heart fills with blood after systole . Ventricular diastole is the period during which the ventricles are relaxing, while atrial diastole is the period during which the atria are relaxing...

), it is also called the diastolic depolarization
Diastolic depolarization
In mammals cardiac electrical activity originates from specialized myocytes of the sinoatrial node which generate spontaneous and rhythmic action potentials . The unique functional aspect of this type of myocyte is the absence of a stable resting potential during diastole...

.
The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K+, Ca2+ , Na+ channels and Na+/K+ exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the “funny”(If) current as one of the most important.(see funny current
Funny current
Funny current refers to a specific current in the heart....

). There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca2+-transients participate to the generation of the diastolic depolarization via a process involving the Na–Ca exchanger.

Distinctions among autonomic foci

In reality, the heart has several pacemakers known as autonomic foci, each which fires at its own intrinsic rate:
  • SA node: 80–100 bpm
  • Atrial foci: 60–80 bpm
  • Junctional foci: 40–60 bpm
  • Ventricular foci: 20–40 bpm


The potentials will normally travel in order

SA node → atrial foci → junctional foci → ventricular foci

Pacemaker potentials are fired not only by SA node, but also by the other foci. However, the other firing frequencies are slower than the one of the SV node (as seen above). Normally, all the foci will end up firing at the SA node rate, not their intrinsic rate. The other foci attempt to fire at their intrinsic rate, but they are activated by the SA node before they can fire. This rapid firing causes all the foci to fire faster than their intrinsic rates, a phenomenon known as overdrive-suppression. Thus, in the normal, healthy heart, only the SA node intrinsic rate is observable.

Pathology

However, in pathological conditions, the intrinsic rate becomes apparent. Consider a heart attack which damages the region of the heart between the SA node and the atrial foci.

SA node → |block| atrial foci → junctional foci → ventricular foci

The other foci will not see the SA node firing; however, they will see the atrial foci. The heart will now beat at the intrinsic rate of the atrial foci.

Induction

The firing of the pacemaker cells is induced electrically by reaching the threshold potential of the cell membrane. The threshold potential
Threshold potential
The threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential.It often can be between −40 and -55 mV, but it can vary based upon several factors...

 is the potential an excitable cell membrane, such as a myocyte
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....

, must reach in order to induce an action potential. This depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...

 is caused by very small net inward currents of calcium ions across the cell membrane, which gives rise to the action potential.

Bio-pacemakers

Bio-pacemakers are the outcome of a rapidly emerging field of research into a replacement for the electronic pacemaker. The bio-pacemaker turns quiescent myocardial cells (e.g. atrial cells) into pacemaker cells. This is achieved by making the cells express a gene which creates a pacemaker current.
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