Hyperpolarization (biology)

Last updated November 21, 2024

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.

Hyperpolarization is often caused by efflux of K⁺ (a cation) through K⁺ channels, or influx of Cl^– (an anion) through Cl^– channels. On the other hand, influx of cations, e.g. Na⁺ through Na⁺ channels or Ca²⁺ through Ca²⁺ channels, inhibits hyperpolarization. If a cell has Na⁺ or Ca²⁺ currents at rest, then inhibition of those currents will also result in a hyperpolarization. This voltage-gated ion channel response is how the hyperpolarization state is achieved. In neurons, the cell enters a state of hyperpolarization immediately following the generation of an action potential. While hyperpolarized, the neuron is in a refractory period that lasts roughly 2 milliseconds (Citation needed here), during which the neuron is unable to generate subsequent action potentials. Sodium-potassium ATPases redistribute K⁺ and Na⁺ ions until the membrane potential is back to its resting potential of around –70 millivolts, at which point the neuron is once again ready to transmit another action potential.^[1]

Voltage-gated ion channels and hyperpolarization

Voltage gated ion channels respond to changes in the membrane potential. Voltage gated potassium, chloride and sodium channels are key components in the generation of the action potential as well as hyper-polarization. These channels work by selecting an ion based on electrostatic attraction or repulsion allowing the ion to bind to the channel.^[2] This releases the water molecule attached to the channel and the ion is passed through the pore. Voltage gated sodium channels open in response to a stimulus and close again. This means the channel either is open or not, there is no part way open. Sometimes the channel closes but is able to be reopened right away, known as channel gating, or it can be closed without being able to be reopened right away, known as channel inactivation.

At resting potential, both the voltage gated sodium and potassium channels are closed but as the cell membrane becomes depolarized the voltage gated sodium channels begin to open up and the neuron begins to depolarize, creating a current feedback loop known as the Hodgkin cycle.^[2] However, potassium ions naturally move out of the cell and if the original depolarization event was not significant enough then the neuron does not generate an action potential. If all the sodium channels are open, however, then the neuron becomes ten times more permeable to sodium than potassium, quickly depolarizing the cell to a peak of +40 mV.^[2] At this level the sodium channels begin to inactivate and voltage gated potassium channels begin to open. This combination of closed sodium channels and open potassium channels leads to the neuron re-polarizing and becoming negative again. The neuron continues to re-polarize until the cell reaches ~ –75 mV,^[2] which is the equilibrium potential of potassium ions. This is the point at which the neuron is hyperpolarized, between –70 mV and –75 mV. After hyperpolarization the potassium channels close and the natural permeability of the neuron to sodium and potassium allows the neuron to return to its resting potential of –70 mV. During the refractory period, which is after hyper-polarization but before the neuron has returned to its resting potential the neuron is capable of triggering an action potential due to the sodium channels ability to be opened, however, because the neuron is more negative it becomes more difficult to reach the action potential threshold.

HCN channels are activated by hyperpolarization.

Recent research has shown that neuronal refractory periods can exceed 20 milliseconds where the relation between hyperpolarization and the neuronal refractory was questioned.^[3]^[4]

Experimental technique

This image shows a model of a patch clamp used in neuroscience. The pipette tip is placed at an ion channel opening and a current is applied and measured using a voltage clamp. Patch pipette model.jpg — This image shows a model of a patch clamp used in neuroscience. The pipette tip is placed at an ion channel opening and a current is applied and measured using a voltage clamp.

Hyperpolarization is a change in membrane potential. Neuroscientists measure it using a technique known as patch clamping that allows them to record ion currents passing through individual channels. This is done using a glass micropipette, also called a patch pipette, with a 1 micrometer diameter. There is a small patch that contains a few ion channels and the rest is sealed off, making this the point of entry for the current. Using an amplifier and a voltage clamp, which is an electronic feedback circuit, allows the experimenter to maintain the membrane potential at a fixed point and the voltage clamp then measures tiny changes in current flow. The membrane currents giving rise to hyperpolarization are either an increase in outward current or a decrease in inward current.^[2]

Examples

Diagram of membrane potential changes during an action potential Apshoot.jpg — Diagram of membrane potential changes during an action potential

During the afterhyperpolarization period after an action potential, the membrane potential is more negative than when the cell is at the resting potential. In the figure to the right, this undershoot occurs at approximately 3 to 4 milliseconds (ms) on the time scale. The afterhyperpolarization is the time when the membrane potential is hyperpolarized relative to the resting potential.
During the rising phase of an action potential, the membrane potential changes from negative to positive, a depolarization. In the figure, the rising phase is from approximately 1 to 2 ms on the graph. During the rising phase, once the membrane potential becomes positive, the membrane potential continues to depolarize (overshoot) until the peak of the action potential is reached at about +40 millivolts (mV). After the peak of the action potential, a hyperpolarization repolarizes the membrane potential to its resting value, first by making it less positive, until 0 mV is reached, and then by continuing to make it more negative. This repolarization occurs in the figure from approximately 2 to 3 ms on the time scale.

Related Research Articles

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.

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

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 $.$

In electrocardiography, the ventricular cardiomyocyte membrane potential is about −90 mV at rest, which is close to the potassium reversal potential. When an action potential is generated, the membrane potential rises above this level in five distinct phases.

Phase 4: Resting membrane potential remains stable at ≈−90 mV.
Phase 0: Rapid depolarisation, shifting the voltage to positive. Specialised membrane proteins in the cell membrane selectively allow sodium ions to enter the cell. This causes the membrane potential to rise at a rate of about 300 V/s. As the membrane voltage rises sodium channels close due to a process called inactivation.
Phase 1: Rapid repolarisation.
Phase 2: Plateau, the longest phase, approximately 100ms.
Phase 3: Rapid repolarisation, which returns the membrane potential to resting potential.

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.

In biology, depolarization or hypopolarization 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.

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.

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.

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).

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.

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.

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.

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.

Visual phototransduction is the sensory transduction process of the visual system by which light is detected by photoreceptor cells in the vertebrate retina. A photon is absorbed by a retinal chromophore, which initiates a signal cascade through several intermediate cells, then through the retinal ganglion cells (RGCs) comprising the optic nerve.

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.

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na⁺) through a cell's membrane. They belong to the superfamily of cation channels.

Afterhyperpolarization, or AHP, is the hyperpolarizing phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phase. AHPs have been segregated into "fast", "medium", and "slow" components that appear to have distinct ionic mechanisms and durations. While fast and medium AHPs can be generated by single action potentials, slow AHPs generally develop only during trains of multiple action potentials.

Low-threshold spikes (LTS) refer to membrane depolarizations by the T-type calcium channel. LTS occur at low, negative, membrane depolarizations. They often follow a membrane hyperpolarization, which can be the result of decreased excitability or increased inhibition. LTS result in the neuron reaching the threshold for an action potential. LTS is a large depolarization due to an increase in Ca²⁺ conductance, so LTS is mediated by calcium (Ca²⁺) conductance. The spike is typically crowned by a burst of two to seven action potentials, which is known as a low-threshold burst. LTS are voltage dependent and are inactivated if the cell's resting membrane potential is more depolarized than −60mV. LTS are deinactivated, or recover from inactivation, if the cell is hyperpolarized and can be activated by depolarizing inputs, such as excitatory postsynaptic potentials (EPSP). LTS were discovered by Rodolfo Llinás and coworkers in the 1980s.

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.

A depolarizing prepulse (DPP) is an electrical stimulus that causes the potential difference measured across a neuronal membrane to become more positive or less negative, and precedes another electrical stimulus. DPPs may be of either the voltage or current stimulus variety and have been used to inhibit neural activity, selectively excite neurons, and increase the pain threshold associated with electrocutaneous stimulation.

References

↑ Pack, Phillip E. "Cliffs AP Biology 3rd Edition"
1 2 3 4 5 Becker, W. M., Kleinsmith, L. J., Hardin, J., & Bertoni, G. P. (2009). Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons. The World of the Cell (7th ed., ). San Francisco: Pearson/Benjamin Cummings.
↑ Vardi, Roni; Tugendhaft, Yael; Sardi, Shira; Kanter, Ido (June 1, 2021). "Significant anisotropic neuronal refractory period plasticity". EPL (Europhysics Letters). 134 (6): 60007. arXiv: 2109.02041 . doi:10.1209/0295-5075/ac177a. ISSN 0295-5075. S2CID 237408101.
↑ Sardi, Shira; Vardi, Roni; Tugendhaft, Yael; Sheinin, Anton; Goldental, Amir; Kanter, Ido (January 3, 2022). "Long anisotropic absolute refractory periods with rapid rise times to reliable responsiveness". Physical Review E. 105 (1): 014401. arXiv: 2111.02689 . Bibcode:2022PhRvE.105a4401S. doi:10.1103/PhysRevE.105.014401. PMID 35193251. S2CID 242757511.