Depolarization

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In biology, depolarization or hypopolarization [1] [2] is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is essential to the function of many cells, communication between cells, and the overall physiology of an organism.

Contents

Action potential in a neuron, showing depolarization, in which the cell's internal charge becomes less negative (more positive), and repolarization, where the internal charge returns to a more negative value. 1221 Action Potential.jpg
Action potential in a neuron, showing depolarization, in which the cell's internal charge becomes less negative (more positive), and repolarization, where the internal charge returns to a more negative value.

Most cells in higher organisms maintain an internal environment that is negatively charged relative to the cell's exterior. This difference in charge is called the cell's membrane potential. In the process of depolarization, the negative internal charge of the cell temporarily becomes more positive (less negative). This shift from a negative to a more positive membrane potential occurs during several processes, including an action potential. During an action potential, the depolarization is so large that the potential difference across the cell membrane briefly reverses polarity, with the inside of the cell becoming positively charged.

The change in charge typically occurs due to an influx of sodium ions into a cell, although it can be mediated by an influx of any kind of cation or efflux of any kind of anion. The opposite of a depolarization is called a hyperpolarization.

Usage of the term "depolarization" in biology differs from its use in physics, where it refers to situations in which any form of polarity (i.e. the presence of any electrical charge, whether positive or negative) changes to a value of zero.

Depolarization is sometimes referred to as "hypopolarization" [1] [2] (as opposed to hyperpolarization).

Physiology

The process of depolarization is entirely dependent upon the intrinsic electrical nature of most cells. When a cell is at rest, the cell maintains what is known as a resting potential. The resting potential generated by nearly all cells results in the interior of the cell having a negative charge compared to the exterior of the cell. To maintain this electrical imbalance, ions are transported across the cell's plasma membrane. [3] The transport of the ions across the plasma membrane is accomplished through several different types of transmembrane proteins embedded in the cell's plasma membrane that function as pathways for ions both into and out of the cell, such as ion channels, sodium potassium pumps, and voltage-gated ion channels.

Resting potential

The resting potential must be established within a cell before the cell can be depolarized. There are many mechanisms by which a cell can establish a resting potential, however there is a typical pattern of generating this resting potential that many cells follow. The generation of a negative resting potential within the cell involves the utilization of ion channels, ion pumps, and voltage-gated ion channels by the cell. [4] However, the process of generating the resting potential within the cell also creates an environment outside the cell that favors depolarization. The sodium potassium pump is largely responsible for the optimization of conditions on both the interior and the exterior of the cell for depolarization.

By pumping three positively charged sodium ions (Na+) out of the cell for every two positively charged potassium ions (K+) pumped into the cell, not only is the resting potential of the cell established, but an unfavorable concentration gradient is created by increasing the concentration of sodium outside the cell and increasing the concentration of potassium within the cell. [5] While there is an excessive amount of potassium in the cell and sodium outside the cell, the generated resting potential maintains the closure of voltage-gated ion channels in the plasma membrane. This not only prevents the diffusion of ions pumped across the membrane but also involves the activity of potassium leak channels, allowing a controlled passive efflux of potassium ions, which contributes to the establishment of the negative resting potential. [6] Additionally, despite the high concentration of positively-charged potassium ions, most cells contain internal components (of negative charge), which accumulate to establish a negative inner charge.

Depolarization

Voltage-gated sodium channel. Open channel (top) carries an influx of Na ions, giving rise to depolarization. As the channel becomes closed/inactivated (bottom), the depolarization ends. Sodium channel open closed.jpg
Voltage-gated sodium channel. Open channel (top) carries an influx of Na ions, giving rise to depolarization. As the channel becomes closed/inactivated (bottom), the depolarization ends.

After a cell has established a resting potential, that cell has the capacity to undergo depolarization. Depolarization is the process by which the membrane potential becomes less negative, facilitating the generation of an action potential. [6] For this rapid change to take place within the interior of the cell, several events must occur along the plasma membrane of the cell.

While the sodium–potassium pump continues to work, the voltage-gated sodium and calcium channels [7] that had been closed while the cell was at resting potential are opened in response to an initial change in voltage. [6] As a change in the neuronal charge leads to the opening of voltage-gated sodium channels, this results in an influx of sodium ions down their electrochemical gradient. Sodium ions enter the cell, and they contribute a positive charge to the cell interior, causing a change in the membrane potential from negative to positive. The initial sodium ion influx triggers the opening of additional sodium channels (positive-feedback loop), leading to further sodium ion transfer into the cell and sustaining the depolarization process until the positive equilibrium potential is reached. [8]

Sodium channels possess an inherent inactivation mechanism that prompts rapid reclosure, even as the membrane remains depolarized. During this equilibrium, the sodium channels enter an inactivated state, temporarily halting the influx of sodium ions until the membrane potential becomes negatively charged again. Once the cell's interior is sufficiently positively charged, depolarization concludes, and the channels close once more. [6]

Repolarization

After a cell has been depolarized, it undergoes one final change in internal charge. Following depolarization, the voltage-gated sodium ion channels that had been open while the cell was undergoing depolarization close again. The increased positive charge within the cell now causes the potassium channels to open. Potassium ions (K+) begin to move down the electrochemical gradient (in favor of the concentration gradient and the newly established electrical gradient). As potassium moves out of the cell the potential within the cell decreases and approaches its resting potential once more. The sodium potassium pump works continuously throughout this process. [9]

Hyperpolarization

The process of repolarization causes an overshoot in the potential of the cell. Potassium ions continue to move out of the axon so much that the resting potential is exceeded and the new cell potential becomes more negative than the resting potential. The resting potential is ultimately re-established by the closing of all voltage-gated ion channels and the activity of the sodium potassium ion pump. [10]

Neurons

Structure of a neuron 1206 The Neuron.jpg
Structure of a neuron

Depolarization is essential to the functions of many cells in the human body, which is exemplified by the transmission of stimuli both within a neuron and between two neurons. The reception of stimuli, neural integration of those stimuli, and the neuron's response to stimuli all rely upon the ability of neurons to utilize depolarization to transmit stimuli either within a neuron or between neurons.

Response to stimulus

Stimuli to neurons can be physical, electrical, or chemical, and can either inhibit or excite the neuron being stimulated. An inhibitory stimulus is transmitted to the dendrite of a neuron, causing hyperpolarization of the neuron. The hyperpolarization following an inhibitory stimulus causes a further decrease in voltage within the neuron below the resting potential. By hyperpolarizing a neuron, an inhibitory stimulus results in a greater negative charge that must be overcome for depolarization to occur.

Excitation stimuli, on the other hand, increase the voltage in the neuron, which leads to a neuron that is easier to depolarize than the same neuron in the resting state. Regardless of it being excitatory or inhibitory, the stimulus travels down the dendrites of a neuron to the cell body for integration.

Integration of stimuli

Summation of stimuli at an axon hillock 1224 Post Synaptic Potential Summation.jpg
Summation of stimuli at an axon hillock

Once the stimuli have reached the cell body, the nerve must integrate the various stimuli before the nerve can respond. The stimuli that have traveled down the dendrites converge at the axon hillock, where they are summed to determine the neuronal response. If the sum of the stimuli reaches a certain voltage, known as the threshold potential, depolarization continues from the axon hillock down the axon.

Response

The surge of depolarization traveling from the axon hillock to the axon terminal is known as an action potential. Action potentials reach the axon terminal, where the action potential triggers the release of neurotransmitters from the neuron. The neurotransmitters that are released from the axon continue on to stimulate other cells such as other neurons or muscle cells. After an action potential travels down the axon of a neuron, the resting membrane potential of the axon must be restored before another action potential can travel the axon. This is known as the recovery period of the neuron, during which the neuron cannot transmit another action potential.

Rod cells of the eye

The importance and versatility of depolarization within cells can be seen in the relationship between rod cells in the eye and their associated neurons. When rod cells are in the dark, they are depolarized. In the rod cells, this depolarization is maintained by ion channels that remain open due to the higher voltage of the rod cell in the depolarized state. The ion channels allow calcium and sodium to pass freely into the cell, maintaining the depolarized state. Rod cells in the depolarized state constantly release neurotransmitters which in turn stimulate the nerves associated with rod cells. This cycle is broken when rod cells are exposed to light; the absorption of light by the rod cell causes the channels that had facilitated the entry of sodium and calcium into the rod cell to close. When these channels close, the rod cells produce fewer neurotransmitters, which is perceived by the brain as an increase in light. Therefore, in the case of rod cells and their associated neurons, depolarization actually prevents a signal from reaching the brain as opposed to stimulating the transmission of the signal. [11] [ page needed ]

Vascular endothelium

Endothelium is a thin layer of simple squamous epithelial cells that line the interior of both blood and lymph vessels. The endothelium that lines blood vessels is known as vascular endothelium, which is subject to and must withstand the forces of blood flow and blood pressure from the cardiovascular system. To withstand these cardiovascular forces, endothelial cells must simultaneously have a structure capable of withstanding the forces of circulation while also maintaining a certain level of plasticity in the strength of their structure. This plasticity in the structural strength of the vascular endothelium is essential to overall function of the cardiovascular system. Endothelial cells within blood vessels can alter the strength of their structure to maintain the vascular tone of the blood vessel they line, prevent vascular rigidity, and even help to regulate blood pressure within the cardiovascular system. Endothelial cells accomplish these feats by using depolarization to alter their structural strength. When an endothelial cell undergoes depolarization, the result is a marked decrease in the rigidity and structural strength of the cell by altering the network of fibers that provide these cells with their structural support. Depolarization in vascular endothelium is essential not only to the structural integrity of endothelial cells, but also to the ability of the vascular endothelium to aid in the regulation of vascular tone, prevention of vascular rigidity, and the regulation of blood pressure. [12]

Heart

Electrocardiogram 2022 Electrocardiogram.jpg
Electrocardiogram

Depolarization occurs in the four chambers of the heart: both atria first, and then both ventricles.

  1. The sinoatrial (SA) node on the wall of the right atrium initiates depolarization in the right and left atria, causing contraction, which corresponds to the P wave on an electrocardiogram.
  2. The SA node sends the depolarization wave to the atrioventricular (AV) node which—with about a 100 ms delay to let the atria finish contracting—then causes contraction in both ventricles, seen in the QRS wave. At the same time, the atria re-polarize and relax.
  3. The ventricles are re-polarized and relaxed at the T wave.

This process continues regularly, unless there is a problem in the heart. [13]

Depolarization blockers

There are drugs, called depolarization blocking agents, that cause prolonged depolarization by opening channels responsible for depolarization and not allowing them to close, preventing repolarization. Examples include the nicotinic agonists, suxamethonium and decamethonium. [14]

Related Research Articles

<span class="mw-page-title-main">Action potential</span> Neuron communication by electric impulses

An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of excitable cells, which include animal cells like neurons and muscle cells, as well as some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells.

<span class="mw-page-title-main">Cardiac pacemaker</span> Network of cells that facilitate rhythmic heart contraction

The contraction of cardiac muscle in all animals is initiated by electrical impulses known as action potentials that in the heart are known as cardiac action potentials. The rate at which these impulses fire controls the rate of cardiac contraction, that is, the heart rate. The cells that create these rhythmic impulses, setting the pace for blood pumping, are called pacemaker cells, and they directly control the heart rate. They make up the cardiac pacemaker, that is, the natural pacemaker of the heart. In most humans, the highest concentration of pacemaker cells is in the sinoatrial (SA) node, the natural and primary pacemaker, and the resultant rhythm is a sinus rhythm.

<span class="mw-page-title-main">Refractory period (physiology)</span> Period of time after an organism performs an action before it is possible to perform again

Refractoriness is the fundamental property of any object of autowave nature not responding to stimuli, if the object stays in the specific refractory state. In common sense, refractory period is the characteristic recovery time, a period that is associated with the motion of the image point on the left branch of the isocline .

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell-to-cell signalling. EPSPs and IPSPs compete with each other at numerous synapses of a neuron. This determines whether an action potential occurring at the presynaptic terminal produces an action potential at the postsynaptic membrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.

Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization. It inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold.

Membrane potential 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 the energy per charge which is required to move a positive charge at constant velocity across the cell membrane from the exterior to the interior.

<span class="mw-page-title-main">Graded potential</span> Changes in membrane potential varying in size

Graded potentials are changes in membrane potential that vary according to the size of the stimulus, as opposed to being all-or-none. They include diverse potentials such as receptor potentials, electrotonic potentials, subthreshold membrane potential oscillations, slow-wave potential, pacemaker potentials, and synaptic potentials. The magnitude of a graded potential is determined by the strength of the stimulus. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space. They do not typically involve voltage-gated sodium and potassium channels, but rather can be produced by neurotransmitters that are released at synapses which activate ligand-gated ion channels. They occur at the postsynaptic dendrite in response to presynaptic neuron firing and release of neurotransmitter, or may occur in skeletal, smooth, or cardiac muscle in response to nerve input. These impulses are incremental and may be excitatory or inhibitory.

<span class="mw-page-title-main">Stimulus (physiology)</span> Detectable change in the internal or external surroundings

In physiology, a stimulus is a detectable change in the physical or chemical structure of an organism's internal or external environment. The ability of an organism or organ to detect external stimuli, so that an appropriate reaction can be made, is called sensitivity (excitability). Sensory receptors can receive information from outside the body, as in touch receptors found in the skin or light receptors in the eye, as well as from inside the body, as in chemoreceptors and mechanoreceptors. When a stimulus is detected by a sensory receptor, it can elicit a reflex via stimulus transduction. An internal stimulus is often the first component of a homeostatic control system. External stimuli are capable of producing systemic responses throughout the body, as in the fight-or-flight response. In order for a stimulus to be detected with high probability, its level of strength must exceed the absolute threshold; if a signal does reach threshold, the information is transmitted to the central nervous system (CNS), where it is integrated and a decision on how to react is made. Although stimuli commonly cause the body to respond, it is the CNS that finally determines whether a signal causes a reaction or not.

<span class="mw-page-title-main">Threshold potential</span> Critical potential value

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 the central nervous system (CNS) and the peripheral nervous system (PNS).

<span class="mw-page-title-main">Axon hillock</span> Part of the neuronal cell soma from which the axon originates

The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance.

<span class="mw-page-title-main">Resting potential</span> Static membrane potential in biology

A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage.

<span class="mw-page-title-main">Cardiac action potential</span> Biological process in the heart

Unlike the action potential in skeletal muscle cells, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as pacemaker cells, that have automatic action potential generation capability. In healthy hearts, these cells form the cardiac pacemaker and are found in the sinoatrial node in the right atrium. They produce roughly 60–100 action potentials every minute. The action potential passes along the cell membrane causing the cell to contract, therefore the activity of the sinoatrial node results in a resting heart rate of roughly 60–100 beats per minute. All cardiac muscle cells are electrically linked to one another, by intercalated discs which allow the action potential to pass from one cell to the next. This means that all atrial cells can contract together, and then all ventricular cells.

<span class="mw-page-title-main">End-plate potential</span> Voltages associated with muscle fibre

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

<span class="mw-page-title-main">Repolarization</span> Change in membrane potential

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of potassium (K+) ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore.

<span class="mw-page-title-main">Voltage-gated ion channel</span> Type of ion channel transmembrane protein

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in a cell's electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels.

The induction of NMDA receptor-dependent long-term potentiation (LTP) in chemical synapses in the brain occurs via a fairly straightforward mechanism. A substantial and rapid rise in calcium ion concentration inside the postsynaptic cell is most possibly all that is required to induce LTP. But the mechanism of calcium delivery to the postsynaptic cell in inducing LTP is more complicated.

<span class="mw-page-title-main">Axolemma</span> Cell membrane of an axon

In neuroscience, the axolemma is the cell membrane of an axon, the branch of a neuron through which signals are transmitted. The axolemma is a three-layered, bilipid membrane. Under standard electron microscope preparations, the structure is approximately 8 nanometers thick.

<span class="mw-page-title-main">Synaptic potential</span> Potential difference across the postsynaptic membrane

Synaptic potential refers to the potential difference across the postsynaptic membrane that results from the action of neurotransmitters at a neuronal synapse. In other words, it is the “incoming” signal that a neuron receives. There are two forms of synaptic potential: excitatory and inhibitory. The type of potential produced depends on both the postsynaptic receptor, more specifically the changes in conductance of ion channels in the post synaptic membrane, and the nature of the released neurotransmitter. Excitatory post-synaptic potentials (EPSPs) depolarize the membrane and move the potential closer to the threshold for an action potential to be generated. Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane and move the potential farther away from the threshold, decreasing the likelihood of an action potential occurring. The Excitatory Post Synaptic potential is most likely going to be carried out by the neurotransmitters glutamate and acetylcholine, while the Inhibitory post synaptic potential will most likely be carried out by the neurotransmitters gamma-aminobutyric acid (GABA) and glycine. In order to depolarize a neuron enough to cause an action potential, there must be enough EPSPs to both depolarize the postsynaptic membrane from its resting membrane potential to its threshold and counterbalance the concurrent IPSPs that hyperpolarize the membrane. As an example, consider a neuron with a resting membrane potential of -70 mV (millivolts) and a threshold of -50 mV. It will need to be raised 20 mV in order to pass the threshold and fire an action potential. The neuron will account for all the many incoming excitatory and inhibitory signals via summative neural integration, and if the result is an increase of 20 mV or more, an action potential will occur.

<span class="mw-page-title-main">Summation (neurophysiology)</span>

Summation, which includes both spatial summation and temporal summation, is the process that determines whether or not an action potential will be generated by the combined effects of excitatory and inhibitory signals, both from multiple simultaneous inputs, and from repeated inputs. Depending on the sum total of many individual inputs, summation may or may not reach the threshold voltage to trigger an action potential.

Cellular neuroscience is a branch of neuroscience concerned with the study of neurons at a cellular level. This includes morphology and physiological properties of single neurons. Several techniques such as intracellular recording, patch-clamp, and voltage-clamp technique, pharmacology, confocal imaging, molecular biology, two photon laser scanning microscopy and Ca2+ imaging have been used to study activity at the cellular level. Cellular neuroscience examines the various types of neurons, the functions of different neurons, the influence of neurons upon each other, and how neurons work together.

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Further reading