Axon hillock
Encyclopedia
The axon hillock is a specialized part of the cell body (or soma
) of a neuron
that connects to the axon
. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed that the axon hillock was the usual site of action potential
initiation. It is now thought that the earliest site of action potential initiation is found just adjacent, in the initial (unmyelinated) segment of the axon
. However, the positive point, at which the action potential starts, varies between cells. It can also be altered by hormonal stimulation of the neuron, or by second messenger effects of neurotransmitters. The axon hillock also functions as a tight junction
, since it acts as a barrier for lateral diffusion of transmembrane proteins, GPI anchored proteins such as thy1, and lipids embedded in the plasma membrane.
Axon hillocks and initial segments have been recognized and studied in electron micrographs
of a wide variety of neurons. In all multipolar neurons the fine structure of the initial segment has the same pattern, whether or not the axon is ensheathed in myelin. .
In dorsal root ganglion
cells, the cell body is thought to have approximately 1 voltage-gated sodium channel per square micrometre, while the axon hillock and initial segment of the axon
have about ~100-200 voltage-gated sodium channels per square micrometre; in comparison, the nodes of Ranvier
along the axon are thought to have ~1000-2000 such channels per square micrometre.
This clustering of voltage-gated ion channels is a consequence of plasma-membrane and cytoskeletal associating proteins such as ankyrin.
). The triggering is due to positive feedback between highly crowded voltage-gated sodium channels, which are present at the critical density at the axon hillock (and nodes of ranvier) but not in the soma.
In its resting state, a neuron is polarized, with its inside at about -70 mV relative to its surroundings. When an excitatory neurotransmitter is released by the presynaptic neuron and binds to the postsynaptic dendritic spines, ligand-gated ion channels open, allowing sodium ions to enter the cell. This may make the postsynaptic membrane depolarized (less negative). This depolarization
will travel towards the axon hillock, diminishing exponentially with time and distance. If several such events occur in a short time, the axon hillock may become sufficiently depolarized for the voltage-gated sodium channels to open. This initiates an action potential that then propagates down the axon.
As sodium enters the cell, the cell membrane potential becomes more positive, which activates even more sodium channels in the membrane. The sodium influx eventually overtakes the potassium efflux (via the potassium leak channels), initiating a positive feedback loop (rising phase). At around +40 mV, the voltage-gated sodium channels begin to close (peak phase) and the voltage-gated potassium channels begin to open, moving potassium against its electrochemical gradient and out of the cell (falling phase). The potassium channels exhibit a delayed reaction to the membrane repolarisation, and, even after the resting potential is achieved, some potassium continues to flow out, resulting in an intracellular fluid that is more negative than the resting potential, and during which no action potential can begin (undershoot phase). This undershoot phase ensures that the action potential propagates down the axon and not back up it. Once this initial action potential is initiated, principally at the axon hillock, it propagates down the length of the axon. Under normal conditions, the action potential would attenuate very quickly due to the porous nature of the cell membrane. To ensure faster and more efficient propagation of action potentials, the axon is myelinated. Myelin, a derivative of cholesterol, acts as an insulating sheath and ensures that the signal cannot escape through the ion or leak channels. There are, nevertheless, gaps in the insulation (nodes of ranvier
), which boost the signal strength. As the action potential reaches a node of Ranvier, it depolarises the cell membrane. As the cell membrane is depolarised, the voltage-gated sodium channels open and sodium rushes in, triggering a fresh new action potential.
See also Initiation Action
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...
) of a neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
that connects to the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed that the axon hillock was the usual site of 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...
initiation. It is now thought that the earliest site of action potential initiation is found just adjacent, in the initial (unmyelinated) segment of the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
. However, the positive point, at which the action potential starts, varies between cells. It can also be altered by hormonal stimulation of the neuron, or by second messenger effects of neurotransmitters. The axon hillock also functions as a tight junction
Tight junction
Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates...
, since it acts as a barrier for lateral diffusion of transmembrane proteins, GPI anchored proteins such as thy1, and lipids embedded in the plasma membrane.
Axon hillocks and initial segments have been recognized and studied in electron micrographs
of a wide variety of neurons. In all multipolar neurons the fine structure of the initial segment has the same pattern, whether or not the axon is ensheathed in myelin. .
Structure
The axon hillock has a number of specialized properties that make it capable of action potential generation, including adjacency to the axon and a much higher density of voltage-gated ion channels than is found in the rest of the cell body. In electrophysiological models, the axon hillock is lumped in with the initial segment of the axon where membrane potentials propagated from synaptic inputs to the dendrites or cell body are summed.In dorsal root ganglion
Dorsal root ganglion
In anatomy and neuroscience, a dorsal root ganglion is a nodule on a dorsal root that contains cell bodies of neurons in afferent spinal nerves.-Unique unipolar structure:...
cells, the cell body is thought to have approximately 1 voltage-gated sodium channel per square micrometre, while the axon hillock and initial segment of the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
have about ~100-200 voltage-gated sodium channels per square micrometre; in comparison, the nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
along the axon are thought to have ~1000-2000 such channels per square micrometre.
This clustering of voltage-gated ion channels is a consequence of plasma-membrane and cytoskeletal associating proteins such as ankyrin.
Function
Both inhibitory postsynaptic potentials (IPSPs) and excitatory postsynaptic potentials (EPSPs) are summed in the axon hillock and once a triggering threshold is exceeded, an action potential propagates through the rest of the axon (and "backwards" towards the dendrites as seen in neural backpropagationNeural backpropagation
Neural backpropagation is the phenomenon in which the action potential of a neuron creates a voltage spike both at the end of the axon and back through to the dendritic arbor or dendrites, from which much of the original input current originated...
). The triggering is due to positive feedback between highly crowded voltage-gated sodium channels, which are present at the critical density at the axon hillock (and nodes of ranvier) but not in the soma.
In its resting state, a neuron is polarized, with its inside at about -70 mV relative to its surroundings. When an excitatory neurotransmitter is released by the presynaptic neuron and binds to the postsynaptic dendritic spines, ligand-gated ion channels open, allowing sodium ions to enter the cell. This may make the postsynaptic membrane depolarized (less negative). 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...
will travel towards the axon hillock, diminishing exponentially with time and distance. If several such events occur in a short time, the axon hillock may become sufficiently depolarized for the voltage-gated sodium channels to open. This initiates an action potential that then propagates down the axon.
As sodium enters the cell, the cell membrane potential becomes more positive, which activates even more sodium channels in the membrane. The sodium influx eventually overtakes the potassium efflux (via the potassium leak channels), initiating a positive feedback loop (rising phase). At around +40 mV, the voltage-gated sodium channels begin to close (peak phase) and the voltage-gated potassium channels begin to open, moving potassium against its electrochemical gradient and out of the cell (falling phase). The potassium channels exhibit a delayed reaction to the membrane repolarisation, and, even after the resting potential is achieved, some potassium continues to flow out, resulting in an intracellular fluid that is more negative than the resting potential, and during which no action potential can begin (undershoot phase). This undershoot phase ensures that the action potential propagates down the axon and not back up it. Once this initial action potential is initiated, principally at the axon hillock, it propagates down the length of the axon. Under normal conditions, the action potential would attenuate very quickly due to the porous nature of the cell membrane. To ensure faster and more efficient propagation of action potentials, the axon is myelinated. Myelin, a derivative of cholesterol, acts as an insulating sheath and ensures that the signal cannot escape through the ion or leak channels. There are, nevertheless, gaps in the insulation (nodes of ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
), which boost the signal strength. As the action potential reaches a node of Ranvier, it depolarises the cell membrane. As the cell membrane is depolarised, the voltage-gated sodium channels open and sodium rushes in, triggering a fresh new action potential.
See also Initiation Action
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...