Cardiac action potential

Drugs affecting the cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing efflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive calcium channels.
Different shapes of the cardiac action potential in various parts of the heart
Action potentials recorded from sheep atrial and ventricular cardiomyocytes with phases shown. Ion currents approximate to ventricular action potential.
Figure 2a: Ventricular action potential (left) and sinoatrial node action potential (right) waveforms. The main ionic currents responsible for the phases are below (upwards deflections represent ions flowing out of cell, downwards deflection represents inward current).
Figure 4: The electrical conduction system of the heart

Brief change in voltage across the cell membrane of heart cells.

- Cardiac action potential

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Action potential

Action potential occurs when the membrane potential of a specific cell location rapidly rises and falls.

As an action potential (nerve impulse) travels down an axon there is a change in electric polarity across the membrane of the axon. In response to a signal from another neuron, sodium- (Na+) and potassium- (K+) gated ion channels open and close as the membrane reaches its threshold potential. Na+ channels open at the beginning of the action potential, and Na+ moves into the axon, causing depolarization. Repolarization occurs when the K+ channels open and K+ moves out of the axon, creating a change in electric polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the axon terminal where it signals other neurons.
Shape of a typical action potential. The membrane potential remains near a baseline level until at some point in time, it abruptly spikes upward and then rapidly falls.
Approximate plot of a typical action potential shows its various phases as the action potential passes a point on a cell membrane. The membrane potential starts out at approximately −70 mV at time zero. A stimulus is applied at time = 1 ms, which raises the membrane potential above −55 mV (the threshold potential). After the stimulus is applied, the membrane potential rapidly rises to a peak potential of +40 mV at time = 2 ms. Just as quickly, the potential then drops and overshoots to −90 mV at time = 3 ms, and finally the resting potential of −70 mV is reestablished at time = 5 ms.
Action potential propagation along an axon
Ion movement during an action potential.
Key: a) Sodium (Na+) ion. b) Potassium (K+) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump. In the stages of an action potential, the permeability of the membrane of the neuron changes. At the resting state (1), sodium and potassium ions have limited ability to pass through the membrane, and the neuron has a net negative charge inside. Once the action potential is triggered, the depolarization (2) of the neuron activates sodium channels, allowing sodium ions to pass through the cell membrane into the cell, resulting in a net positive charge in the neuron relative to the extracellular fluid. After the action potential peak is reached, the neuron begins repolarization (3), where the sodium channels close and potassium channels open, allowing potassium ions to cross the membrane into the extracellular fluid, returning the membrane potential to a negative value. Finally, there is a refractory period (4), during which the voltage-dependent ion channels are inactivated while the Na+ and K+ ions return to their resting state distributions across the membrane (1), and the neuron is ready to repeat the process for the next action potential.
When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of neurotransmitter molecules that open ion channels in the post-synaptic neuron (bottom). The combined excitatory and inhibitory postsynaptic potentials of such inputs can begin a new action potential in the post-synaptic neuron.
In pacemaker potentials, the cell spontaneously depolarizes (straight line with upward slope) until it fires an action potential.
In saltatory conduction, an action potential at one node of Ranvier causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node.
Comparison of the conduction velocities of myelinated and unmyelinated axons in the cat. The conduction velocity v of myelinated neurons varies roughly linearly with axon diameter d (that is, v ∝ d), whereas the speed of unmyelinated neurons varies roughly as the square root (v ∝√d). The red and blue curves are fits of experimental data, whereas the dotted lines are their theoretical extrapolations.
Cable theory's simplified view of a neuronal fiber. The connected RC circuits correspond to adjacent segments of a passive neurite. The extracellular resistances re (the counterparts of the intracellular resistances ri) are not shown, since they are usually negligibly small; the extracellular medium may be assumed to have the same voltage everywhere.
Electrical synapses between excitable cells allow ions to pass directly from one cell to another, and are much faster than chemical synapses.
Phases of a cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive calcium channels.
Giant axons of the longfin inshore squid (Doryteuthis pealeii) were crucial for scientists to understand the action potential.
As revealed by a patch clamp electrode, an ion channel has two states: open (high conductance) and closed (low conductance).
Tetrodotoxin is a lethal toxin found in pufferfish that inhibits the voltage-sensitive sodium channel, halting action potentials.
Image of two Purkinje cells (labeled as A) drawn by Santiago Ramón y Cajal in 1899. Large trees of dendrites feed into the soma, from which a single axon emerges and moves generally downwards with a few branch points. The smaller cells labeled B are granule cells.
Ribbon diagram of the sodium–potassium pump in its E2-Pi state. The estimated boundaries of the lipid bilayer are shown as blue (intracellular) and red (extracellular) planes.
Equivalent electrical circuit for the Hodgkin–Huxley model of the action potential. Im and Vm represent the current through, and the voltage across, a small patch of membrane, respectively. The Cm represents the capacitance of the membrane patch, whereas the four g's represent the conductances of four types of ions. The two conductances on the left, for potassium (K) and sodium (Na), are shown with arrows to indicate that they can vary with the applied voltage, corresponding to the voltage-sensitive ion channels. The two conductances on the right help determine the resting membrane potential.

In cardiac muscle cells, on the other hand, an initial fast sodium spike provides a "primer" to provoke the rapid onset of a calcium spike, which then produces muscle contraction.

Potassium channel

Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms.

Potassium channel Kv1.2, structure in a membrane-like environment. Calculated hydrocarbon boundaries of the lipid bilayer are indicated by red and blue lines.
Top view of a potassium channel with potassium ions (purple) moving through the pore (in the center).
Crystallographic structure of the bacterial KcsA potassium channel . In this figure, only two of the four subunits of the tetramer are displayed for the sake of clarity. The protein is displayed as a green cartoon diagram. In addition backbone carbonyl groups and threonine sidechain protein atoms (oxygen = red, carbon = green) are displayed. Finally potassium ions (occupying the S2 and S4 sites) and the oxygen atoms of water molecules (S1 and S3) are depicted as purple and red spheres respectively.
Graphical representation of open and shut potassium channels ( and ). Two simple bacterial channels are shown to compare the "open" channel structure on the right with the "closed" structure on the left. At top is the filter (selects potassium ions), and at bottom is the gating domain (controls opening and closing of channel).
Birth of an Idea (2007) by Julian Voss-Andreae. The sculpture was commissioned by Roderick MacKinnon based on the molecule's atomic coordinates that were determined by MacKinnon's group in 2001.

By contributing to the regulation of the cardiac action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias.

Sinoatrial node

Group of cells known as pacemaker cells, located in the wall of the right atrium of the heart.

Sinoatrial node shown at 1. The rest of the conduction system of the heart is shown in blue.
Figure 2: Low magnification stained image of the SA node (center-right on image) and its surrounding tissue. The SA node surrounds the sinoatrial nodal artery, seen as the open lumen. Cardiac muscle cells of the right atrium can be seen to the left of the node, and fat tissue to the right.
Figure 3: Sinoatrial node action potential waveform, outlining major ion currents involved (downward deflection indicates ions moving into the cell, upwards deflection indicates ions flowing out of the cell).
Schematic representation of the atrioventricular bundle

This resting phase (see cardiac action potential, phase 4) ends when an action potential reaches the cell.

Cardiac muscle

One of three types of vertebrate muscle tissue, with the other two being skeletal muscle and smooth muscle.

3D rendering showing thick myocardium within the heart wall.
The swirling musculature of the heart ensures effective pumping of blood.
Cardiac muscle
Illustration of a cardiac muscle cell.
Intercalated discs are part of the cardiac muscle cell sarcolemma and they contain gap junctions and desmosomes.
Dog cardiac muscle (400X)

Electrical stimulation in the form of a cardiac action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum.

Arrhythmia

Too fast or too slow.

Ventricular fibrillation (VF) showing disorganized electrical activity producing a spiked tracing on an electrocardiogram (ECG)
Broad classification of arrhythmias according to region of heart required to sustain the rhythm
Normal sinus rhythm, with solid black arrows pointing to normal P waves representative of normal sinus node function, followed by a pause in sinus node activity (resulting in a transient loss of heartbeats). Note that the P wave that disrupts the pause (indicated by the dashed arrow) does not look like the previous (normal) P waves – this last P wave is arising from a different part of the atrium, representing an escape rhythm.

The first of arrhythmia is a result of enhanced or abnormal impulse formation originating at the pacemaker or the His-Purkinje network.

HERG

Gene that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel.

Rendering of HLA-A11 showing the α (A*1101 gene product) and β (Beta-2 microglobulin) subunits. This receptor has a bound peptide (in the binding pocket) of heterologous origin that also contributes to function.

This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution to the electrical activity of the heart: the hERG channel mediates the repolarizing IKr current in the cardiac action potential, which helps coordinate the heart's beating.

Sodium-calcium exchanger

Antiporter membrane protein that removes calcium from cells.

Comparison of transport proteins

The ability for the Na+/Ca2+ exchanger to reverse direction of flow manifests itself during the cardiac action potential.

Purkinje fibers

The Purkinje fibers (often incorrectly ; Purkinje tissue or subendocardial branches) are located in the inner ventricular walls of the heart, just beneath the endocardium in a space called the subendocardium.

Isolated heart conduction system showing Purkinje fibers
Purkinje fiber just beneath the endocardium.

They conduct cardiac action potentials more quickly and efficiently than any other cells in the heart.

Pacemaker potential

Slow, positive increase in voltage across the cell's membrane (the membrane potential) that occurs between the end of one action potential and the beginning of the next action potential.

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Pacemaker rates

This increase in membrane potential is what causes the cell membrane, which typically maintains a resting membrane potential of -70 mV, to reach the threshold potential 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.

Cardiac transient outward potassium current

One of the ion currents across the cell membrane of heart muscle cells.

The cardiac action potential has five phases. Ito1 is active during phase 1, causing a fast repolarization of the action potential

It is the main contributing current during the repolarizing phase 1 of the cardiac action potential.