In the pacemaking cells of the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

(e.g., the

sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node, sinus node or Keith–Flack node) is an ellipse, oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of Cell (biology), cells known as pa ...

), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane, that occurs between the end of one

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

and the beginning of the next. It is responsible for the self-generated rhythmic firing (

automaticity In the field of psychology, automaticity is the ability to do things without occupying the mind with the low-level details required, allowing it to become an automatic response pattern or habit. It is usually the result of learning, repetition, ...

) of pacemaker cells.

Background

The cardiac pacemaker is the

's natural rhythm generator. It employs pacemaker cells that generate electrical impulses, known as cardiac action potentials. These potentials cause the

cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

to contract, and the rate of which these muscles contract determines the

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

. As with any other cells, pacemaker cells have an electrical charge on their membranes. This electrical charge is called the

membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is th ...

. After the firing of an action potential, the pacemaking cell's membrane repolarizes (decreases in voltage) to its

resting potential The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential. The re ...

of -60 mV. From here, the membrane gradually depolarizes (increases in voltage) to the

threshold potential In electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both ...

of -40 mV, upon which the cell would go on to fire the next action potential. The rate of depolarization is the slope: the faster voltage increases, the steeper the slopes are in graphs. The slope determines the time taken to reach the threshold potential, and thus the timing of the next action potential. 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 ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are refilling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricul ...

), it is also called the diastolic depolarization. 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”(I_f) current as one of the most important. (see

funny current The pacemaker current (I''f'', or IK''f'', also called funny current) is an electric current in the heart that flows through the HCN channel or pacemaker channel. Such channels are important parts of the electrical conduction system of the heart an ...

). 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. The rhythmic activity of some

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

like the pre-Bötzinger complex is modulated by neurotransmitters and neuropeptides, and such modulatory connectivity gives to the neurons the necessary plasticity to generating distinctive, state-dependent rhythmic patterns that depend on pacemaker potentials.

Pacemakers

The heart has several pacemakers, each which fires at its own intrinsic rate: * ''SA node:'' 60–100 bpm * ''Atrioventricular node(AVN):'' 40–60 bpm * ''Purkinje fibres:'' 20–40 bpm The potentials will normally travel in order
SA node → Atrioventricular node → Purkinje fibres Normally, all the foci will end up firing at the SA node rate, not their intrinsic rate in 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 AV node. SA node → , block, AV node → Purkinje fibres 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 AV node.

Induction

The firing of the pacemaker cells is induced electrically by reaching the threshold potential of the cell membrane. The

is the potential an excitable cell membrane, such as a

myocyte A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...

, must reach in order to induce an action potential. This

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

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.

References