Gating (electrophysiology)

Last updated
An animated representation of the molecular structure of a simple ion channel PDB 1av2 EBI.jpg
An animated representation of the molecular structure of a simple ion channel

In electrophysiology, the term gating refers to the opening (activation) or closing (by deactivation or inactivation) of ion channels. [1] This change in conformation is a response to changes in transmembrane voltage. [2]

Contents

When ion channels are in a 'closed' (non-conducting) state, they are impermeable to ions and do not conduct electrical current. When ion channels are in their open state, they conduct electrical current by allowing specific types of ions to pass through them, and thus, across the plasma membrane of the cell. Gating is the process by which an ion channel transitions between its open and closed states. [3]

A variety of cellular changes can trigger gating, depending on the ion channel, including changes in voltage across the cell membrane (voltage-gated ion channels), chemicals interacting with the ion channel (ligand-gated ion channels), changes in temperature, [4] stretching or deformation of the cell membrane, addition of a phosphate group to the ion channel (phosphorylation), and interaction with other molecules in the cell (e.g., G proteins). [5] The rate at which any of these gating processes occurs in response to these triggers are known as the kinetics of gating. Some drugs and many ion channel toxins act as 'gating modifiers' of voltage-gated ion channels by changing the kinetics of gating. [6]

The voltage-gated ion channels of the action potential are often described as having four gating processes: activation, deactivation, inactivation, and reactivation (also called 'recovery from inactivation'). Activation is the process of opening the activation gate, which occurs in response to the voltage inside the cell membrane (the membrane potential) becoming more positive with respect to the outside of the cell (depolarization), and 'deactivation' is the opposite process of the activation gate closing in response to the inside of the membrane becoming more negative (repolarization). 'Inactivation' is the closing of the inactivation gate, and occurs in response to the voltage inside the membrane becoming more positive, but more slowly than activation. 'Reactivation' is the opposite of inactivation, and is the process of reopening the inactivation gate. [7]

These voltage-dependent changes in function are critical for a large number of processes in excitable and nonexcitable cells. [2]

Activation

Voltage-gated ion channels

Voltage-gated ion channel. When the membrane is polarized, the voltage sensing domain of the channel shifts, opening the channel to ion flow (ions represented by yellow circles). Voltage-gated Ion Channel.png
Voltage-gated ion channel. When the membrane is polarized, the voltage sensing domain of the channel shifts, opening the channel to ion flow (ions represented by yellow circles).

Voltage-gated ion channels open and close in response to the electrical potential across the cell membrane. Portions of the channel domain act as voltage sensors. As the membrane potential changes, this results in changes in electrostatic forces, moving these voltage-sensing domains. This changes the conformation of other elements of the channel to either the open or closed position. [8] When they move from the closed position to the open position, this is called "activation." Voltage-gated ion channels underlie many of the electrical behaviors of the cell, including action potentials, resting membrane potentials, and synaptic transmission. [9]

Voltage-gated ion channels are often specific to ions, including Na+, K+, Ca2+, and Cl−. Each of these ions plays an important role in the electrical behavior of the cell. [9] The gates also have unique properties with important physiological implications. For example, Na+ channels open and close rapidly, while K+ gates open and close much more slowly. The difference in speed between these channels underlies the depolarization and repolarization phases of the action potential. [10]

Na+ Channels

Voltage Gated Sodium (Na+) channels are significant when it comes to propagating the action potentials in neurons and other excitable cells, mostly being used for the propagation of action potential in axons, muscle fibers and the neural somatodendritic compartment. [11] Sodium(Na+) channels are some of the main ion channels responsible for action potentials. [9] Being complex, they are made of bigger α subunits that are then paired with two smaller β subunits. [11] They contain transmembrane segments known as S1-6. The charged S4 segments are the channels voltage sensors. When exposed to a certain minimum potential difference, the S4 segments move across the membrane. [12] This causes movement of the S4-S5 linker, which causes the S5-S6 linker to twist and opens the channel. [13]

K+ Channels

Potassium (K+) channels play a large role in setting the resting membrane potential. [9] When the cell membrane depolarizes, the intracellular part of the channel becomes positively charged, which causes the channel's open configuration to become a more stable state than the closed configuration. There are a few models of potassium channel activation:

  • The sliding helix model posits that the potassium channel opens due to a screwing motion by its S4 helix.
  • The paddle model posits that the S3 and S4 helices of the channel form "paddles" that move through the depolarized membrane and pull the S5 helix away from the channel's opening.
  • The transport model posits that a focused electric field causes charged particles to move across the channel with only a small movement of the S4 helix.
  • The model of coordinated movement of helices posits that the S4 and S5 helices both rotate, and the S4-S5 linker causes the S6 helix to move, opening the channel.
  • The consensus model is an average of the above models that helps reconcile them with experimental data. [14]

Ca2+ Channels

Calcium (Ca2+) channels regulate the release of neurotransmitters at synapses, control the shape of action potentials made by sodium channels, and in some neurons, generate action potentials. [9] Calcium channels consist of six transmembrane helices. S4 acts as the voltage sensor by rotating when exposed to certain membrane potentials, thereby opening the channel. [15]

Calcium release causes a strong attraction between multiple proteins including synaptobrevin and SNARE proteins to pull the neurotransmitter vesicle to the membrane and release its contents into the synaptic cleft Opening of a Fusion Pore during Exocytosis.png
Calcium release causes a strong attraction between multiple proteins including synaptobrevin and SNARE proteins to pull the neurotransmitter vesicle to the membrane and release its contents into the synaptic cleft

Neurotransmitters are initially stored and synthesized in vesicles at the synapse of a neuron. When an action potential occurs in a cell, the electrical signal reaches the presynaptic terminal and the depolarization causes calcium channels to open, releasing calcium to travel down its electrochemical gradient. This influx of calcium subsequently is what causes the neurotransmitter vesicles to fuse with the presynaptic membrane. [16] The calcium ions initiate the interaction of obligatory cofactor proteins with SNARE proteins to form a SNARE complex. [16] These SNARE complexes mediate vesicle fusion by pulling the membranes together, leaking the neurotransmitters into the synaptic cleft. The neurotransmitter molecules can then signal the next cell via receptors on the post synaptic membrane. These receptors can either act as ion channels or GPCR (G-Protein Coupled Receptors). [17] In general the neurotransmitter can either cause an excitatory or inhibitory response, depending on what occurs at the receptor.

Cl− Channels

Chloride channels are another group of voltage gated ion channels, of which are less understood. They are involved with processes such as skeletal and cardiac smooth muscle, cell volume regulation, the cell cycle, and apoptosis. [18] One major family of chloride proteins are called CLC proteins, functionally categories into channel or transporter. [19] They share homodimeric structure with independent ion permeation pathway in each of the subunit. [20] Based on functional characterization, there are two known gating mechanism: protopore and common gating. The protopore gating, also known as fast gating, is associated with occlusion of the pore via side-chain of conserved glutamate. While the common gating, also known as the slow gating, inactivated or reactivates both pores through unknown mechanism. [21] This family either transports two chloride for one proton or simply allows flux down its electrochemical gradient. [22] With this channel the correct depolarization and repolarization via chloride ions is essential for propagation of an action potential. [18]

Ligand-gated ion channels

Ligand-gated ion channels are found on postsynaptic neurons. By default, they assume their closed conformation. When the presynaptic neuron releases neurotransmitters at the end of an action potential, they bind to ligand-gated ion channels. This causes the channels to assume their open conformation, allowing ions to flow through the channels down their concentration gradient. Ligand-gated ion channels are responsible for fast synaptic transmission in the nervous system and at the neuromuscular junction. [23] Each ligand-gated ion channel has a wide range of receptors with differing biophysical properties as well as patterns of expression in the nervous system. [24]

Inactivation

Inactivation is when the flow of ions is blocked by a mechanism other than the closing of the channel. [8] A channel in its open state may stop allowing ions to flow through, or a channel in its closed state may be preemptively inactivated to prevent the flow of ions. [25] Inactivation typically occurs when the cell membrane depolarize, and ends when the resting potential is restored. [8]

In sodium channels, inactivation appears to be the result of the actions of helices III-VI, with III and IV acting as a sort of hinged lid that block the channel. The exact mechanism is poorly understood, but seems to rely on a particle that has a high affinity for the exposed inside of the open channel. [26] Rapid inactivation allows the channel to halt the flow of sodium very shortly after assuming its open conformation. [27]

Ball and chain inactivation

Voltage-gated ion channel in its closed, open, and inactivated states. The inactivated channel is still in its open state, but the ball domain blocks ion permeation. Ball and Chain Voltage-gated Ion Channel.png
Voltage-gated ion channel in its closed, open, and inactivated states. The inactivated channel is still in its open state, but the ball domain blocks ion permeation.

The ball and chain model, also known as N-type inactivation or hinged lid inactivation, is a gating mechanism for some voltage-gated ion channels. Voltage-gated ion channels are composed of 4[ dubious – discuss ] α subunits, one or more of which will have a ball domain located on its cytoplasmic N-terminus. [28] The ball domain is electrostatically attracted to the inner channel domain. When the ion channel is activated, the inner channel domain is exposed, and within milliseconds the chain will fold and the ball will enter the channel, occluding ion permeation. [29] The channel returns to its closed state, blocking the channel domain, and the ball leaves the pore. [30]

Deactivation

As the membrane potential returns to its resting value, the voltage differential is not sufficient to keep the channel in its open state, causing the channel to close. Deactivation of Voltage-gated ion channel.png
As the membrane potential returns to its resting value, the voltage differential is not sufficient to keep the channel in its open state, causing the channel to close.

Deactivation is the return of an ion channel to its closed conformation. For voltage-gated channels this occurs when the voltage differential that originally caused the channel to open returns to its resting value. [31]

In voltage-gated sodium channels, deactivation is necessary to recover from inactivation. [26]

In voltage gated potassium channels, the reverse is true, and deactivation slows the channel's recovery from activation. [32] The closed conformation is assumed by default, and involves the partial straightening of helix VI by the IV-V linker. The mechanisms that cause opening and closing are not fully understood. The closed conformation appears to be a higher energy conformation than the open conformation, which may also help explain how the ion channel activates. [33]

Quantification

Gating charge can be calculated by solving Poisson's equation. Recent studies have suggested a molecular dynamics simulation-based method to determine gating charge by measuring electrical capacitor properties of membrane-embedded proteins. [2] Activity of ion channels located in the plasma membrane can be measured by simply attaching a glass capillary electrode continuously with the membrane. [34] Other ion channels located in the membranes of mitochondria, lysosomes, and the Golgi apparatus can be measured by an emergent technique that involves the use of an artificial bilayer lipid membrane attached to a 16 electrode device that measures electrical activity. [34]

See also

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

<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 animal cells, called excitable cells, which include neurons, muscle cells, and in 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 .

<span class="mw-page-title-main">BK channel</span> Family of transport proteins

BK channels (big potassium), are large conductance calcium-activated potassium channels, also known as Maxi-K, slo1, or Kca1.1. BK channels are voltage-gated potassium channels that conduct large amounts of potassium ions (K+) across the cell membrane, hence their name, big potassium. These channels can be activated (opened) by either electrical means, or by increasing Ca2+ concentrations in the cell. BK channels help regulate physiological processes, such as circadian behavioral rhythms and neuronal excitability. BK channels are also involved in many processes in the body, as it is a ubiquitous channel. They have a tetrameric structure that is composed of a transmembrane domain, voltage sensing domain, potassium channel domain, and a cytoplasmic C-terminal domain, with many X-ray structures for reference. Their function is to repolarize the membrane potential by allowing for potassium to flow outward, in response to a depolarization or increase in calcium levels.

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.

<span class="mw-page-title-main">Membrane potential</span> Type of physical quantity

Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges to move from the internal to exterior cellular environments and vice versa, as long as there is no acquisition of kinetic energy or the production of radiation. The concentration gradients of the charges directly determine this energy requirement. For the exterior of the cell, typical values of membrane potential, normally given in units of milli volts and denoted as mV, range from –80 mV to –40 mV.

<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.

Inorganic ions in animals and plants are ions necessary for vital cellular activity. In body tissues, ions are also known as electrolytes, essential for the electrical activity needed to support muscle contractions and neuron activation. They contribute to osmotic pressure of body fluids as well as performing a number of other important functions. Below is a list of some of the most important ions for living things as well as examples of their functions:

<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 the 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. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+–Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

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.

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.

<span class="mw-page-title-main">Voltage-gated potassium channel</span> Class of transport proteins

Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state.

T-type calcium channels are low voltage activated calcium channels that become inactivated during cell membrane hyperpolarization but then open to depolarization. The entry of calcium into various cells has many different physiological responses associated with it. Within cardiac muscle cell and smooth muscle cells voltage-gated calcium channel activation initiates contraction directly by allowing the cytosolic concentration to increase. Not only are T-type calcium channels known to be present within cardiac and smooth muscle, but they also are present in many neuronal cells within the central nervous system. Different experimental studies within the 1970s allowed for the distinction of T-type calcium channels from the already well-known L-type calcium channels. The new T-type channels were much different from the L-type calcium channels due to their ability to be activated by more negative membrane potentials, had small single channel conductance, and also were unresponsive to calcium antagonist drugs that were present. These distinct calcium channels are generally located within the brain, peripheral nervous system, heart, smooth muscle, bone, and endocrine system.

<span class="mw-page-title-main">L-type calcium channel</span> Family of transport proteins

The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.

<span class="mw-page-title-main">Channel blocker</span> Molecule able to block protein channels, frequently used as pharmaceutical

A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.

<span class="mw-page-title-main">Dendritic spike</span> Action potential generated in the dendrite of a neuron

In neurophysiology, a dendritic spike refers to an action potential generated in the dendrite of a neuron. Dendrites are branched extensions of a neuron. They receive electrical signals emitted from projecting neurons and transfer these signals to the cell body, or soma. Dendritic signaling has traditionally been viewed as a passive mode of electrical signaling. Unlike its axon counterpart which can generate signals through action potentials, dendrites were believed to only have the ability to propagate electrical signals by physical means: changes in conductance, length, cross sectional area, etc. However, the existence of dendritic spikes was proposed and demonstrated by W. Alden Spencer, Eric Kandel, Rodolfo Llinás and coworkers in the 1960s and a large body of evidence now makes it clear that dendrites are active neuronal structures. Dendrites contain voltage-gated ion channels giving them the ability to generate action potentials. Dendritic spikes have been recorded in numerous types of neurons in the brain and are thought to have great implications in neuronal communication, memory, and learning. They are one of the major factors in long-term potentiation.

References

  1. ↑ Alberts, Bruce; Bray, Dennis; Lewis, Julian; Raff, Martin; Roberts, Keith; Watson, James D. (1994). Molecular biology of the cell . New York: Garland. pp.  523–547. ISBN   978-0-8153-1620-6.
  2. 1 2 3 Machtens, Jan-Philipp; Briones, Rodolfo; Alleva, Claudia; de Groot, Bert L.; Fahlke, Christoph (2017-04-11). "Gating Charge Calculations by Computational Electrophysiology Simulations". Biophysical Journal. 112 (7): 1396–1405. Bibcode:2017BpJ...112.1396M. doi:10.1016/j.bpj.2017.02.016. ISSN   0006-3495. PMC   5389965 . PMID   28402882.
  3. ↑ Goychuk, Igor; Hänggi, Peter (2002-03-19). "Ion channel gating: A first-passage time analysis of the Kramers type". Proceedings of the National Academy of Sciences of the United States of America. 99 (6): 3552–3556. arXiv: physics/0111187 . Bibcode:2002PNAS...99.3552G. doi: 10.1073/pnas.052015699 . ISSN   0027-8424. PMC   122561 . PMID   11891285.
  4. ↑ Cesare P, Moriondo A, Vellani V, McNaughton PA (July 1999). "Ion channels gated by heat". Proc. Natl. Acad. Sci. U.S.A. 96 (14): 7658–63. Bibcode:1999PNAS...96.7658C. doi: 10.1073/pnas.96.14.7658 . PMC   33597 . PMID   10393876.
  5. ↑ Hille, Bertil (2001). Ion channels of excitable membranes. Sunderland, Mass: Sinauer. ISBN   978-0-87893-321-1.
  6. ↑ Waszkielewicz, A.M; Gunia, A; Szkaradek, N; Słoczyńska, K; Krupińska, S; Marona, H (April 2013). "Ion Channels as Drug Targets in Central Nervous System Disorders". Current Medicinal Chemistry. 20 (10): 1241–1285. doi:10.2174/0929867311320100005. ISSN   0929-8673. PMC   3706965 . PMID   23409712.
  7. ↑ Ahern, Christopher A.; Payandeh, Jian; Bosmans, Frank; Chanda, Baron (January 2016). "The hitchhiker's guide to the voltage-gated sodium channel galaxy". The Journal of General Physiology. 147 (1): 1–24. doi:10.1085/jgp.201511492. ISSN   0022-1295. PMC   4692491 . PMID   26712848.
  8. 1 2 3 Bähring, Robert; Covarrubias, Manuel (2011-02-01). "Mechanisms of closed-state inactivation in voltage-gated ion channels". The Journal of Physiology. 589 (Pt 3): 461–479. doi:10.1113/jphysiol.2010.191965. ISSN   0022-3751. PMC   3055536 . PMID   21098008.
  9. 1 2 3 4 5 Purves, Dale; Augustine, George J.; Fitzpatrick, David; Katz, Lawrence C.; LaMantia, Anthony-Samuel; McNamara, James O.; Williams, S. Mark (2001). "Voltage-Gated Ion Channels". Neuroscience. 2nd Edition.
  10. ↑ Grider, Michael H.; Glaubensklee, Carolyn S. (2019), "Physiology, Action Potential", StatPearls, StatPearls Publishing, PMID   30844170 , retrieved 2019-10-29
  11. 1 2 Mantegazza, Massimo; Catterall, William A. (2012), Noebels, Jeffrey L.; Avoli, Massimo; Rogawski, Michael A.; Olsen, Richard W. (eds.), "Voltage-Gated Na+ Channels: Structure, Function, and Pathophysiology", Jasper's Basic Mechanisms of the Epilepsies (4th ed.), National Center for Biotechnology Information (US), PMID   22787615 , retrieved 2019-11-03
  12. ↑ Sula, Altin; Booker, Jennifer; Ng, Leo C. T.; Naylor, Claire E.; DeCaen, Paul G.; Wallace, B. A. (2017-02-16). "The complete structure of an activated open sodium channel". Nature Communications. 8 (1): 14205. Bibcode:2017NatCo...814205S. doi:10.1038/ncomms14205. ISSN   2041-1723. PMC   5316852 . PMID   28205548.
  13. ↑ Catterall, William A. (2013-11-14). "Structure and function of voltage-gated sodium channels at atomic resolution". Experimental Physiology. 99 (1): 35–51. doi:10.1113/expphysiol.2013.071969. ISSN   0958-0670. PMC   3885250 . PMID   24097157.
  14. ↑ Grizel, A. V.; Glukhov, G. S.; Sokolova, O. S. (Oct–Dec 2014). "Mechanisms of Activation of Voltage-Gated Potassium Channels". Acta Naturae. 6 (4): 10–26. doi:10.32607/20758251-2014-6-4-10-26. PMC   4273088 . PMID   25558391.
  15. ↑ Catterall, William A. (August 2011). "Voltage-Gated Calcium Channels". Cold Spring Harbor Perspectives in Biology. 3 (8): a003947. doi:10.1101/cshperspect.a003947. ISSN   1943-0264. PMC   3140680 . PMID   21746798.
  16. 1 2 Südhof, Thomas C. (January 2012). "Calcium Control of Neurotransmitter Release". Cold Spring Harbor Perspectives in Biology. 4 (1): a011353. doi:10.1101/cshperspect.a011353. ISSN   1943-0264. PMC   3249630 . PMID   22068972.
  17. ↑ Yoon, Tae-Young; Lu, Xiaobing; Diao, Jiajie; Lee, Soo-Min; Ha, Taekjip; Shin, Yeon-Kyun (June 2008). "Complexin and Ca 2+ stimulate SNARE-mediated membrane fusion". Nature Structural & Molecular Biology. 15 (7): 707–713. doi:10.1038/nsmb.1446. ISSN   1545-9985. PMC   2493294 . PMID   18552825.
  18. 1 2 "Chloride channels". British Journal of Pharmacology. 158 (Suppl 1): S130–S134. November 2009. doi:10.1111/j.1476-5381.2009.00503_6.x. ISSN   0007-1188. PMC   2884561 .
  19. ↑ Kwon, Hwoi Chan; Fairclough, Robert H.; Chen, Tsung-Yu (2022), "Biophysical and Pharmacological Insights to CLC Chloride Channels", Anion Channels and Transporters, Handbook of Experimental Pharmacology, vol. 283, Berlin, Heidelberg: Springer, pp. 1–34, doi:10.1007/164_2022_594, ISBN   978-3-031-51345-9, PMID   35768555 , retrieved 2023-04-27
  20. ↑ Park, Eunyong; MacKinnon, Roderick (2018-05-29). Csanády, László (ed.). "Structure of the CLC-1 chloride channel from Homo sapiens". eLife. 7: e36629. doi: 10.7554/eLife.36629 . ISSN   2050-084X. PMC   6019066 . PMID   29809153.
  21. ↑ Jentsch, Thomas J.; Pusch, Michael (2018-07-01). "CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease". Physiological Reviews. 98 (3): 1493–1590. doi: 10.1152/physrev.00047.2017 . ISSN   0031-9333. PMID   29845874. S2CID   44165561.
  22. ↑ Accardi, Alessio; Picollo, Alessandra (August 2010). "CLC channels and transporters: proteins with borderline personalities". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1798 (8): 1457–1464. doi:10.1016/j.bbamem.2010.02.022. ISSN   0006-3002. PMC   2885512 . PMID   20188062.
  23. ↑ Alexander, SPH; Mathie, A; Peters, JA (November 2011). "Ligand-Gated Ion Channels". British Journal of Pharmacology. 164 (Suppl 1): S115–S135. doi:10.1111/j.1476-5381.2011.01649_4.x. ISSN   0007-1188. PMC   3315629 .
  24. ↑ Alexander, SPH; Mathie, A; Peters, JA (2011). "Ligand-Gated Ion Channels". Br J Pharmacol. 164 (Suppl 1): S115–S135. doi:10.1111/j.1476-5381.2011.01649_4.x. PMC   3315629 .
  25. ↑ Armstrong, Clay M. (2006-11-21). "Na channel inactivation from open and closed states". Proceedings of the National Academy of Sciences. 103 (47): 17991–17996. Bibcode:2006PNAS..10317991A. doi: 10.1073/pnas.0607603103 . ISSN   0027-8424. PMC   1693860 . PMID   17101981.
  26. 1 2 Kuo, Chung-Chin; Bean, Bruce P. (1994-04-01). "Na+ channels must deactivate to recover from inactivation". Neuron. 12 (4): 819–829. doi:10.1016/0896-6273(94)90335-2. ISSN   0896-6273. PMID   8161454. S2CID   41285799.
  27. ↑ Yu, Frank H; Catterall, William A (2003). "Overview of the voltage-gated sodium channel family". Genome Biology. 4 (3): 207. doi: 10.1186/gb-2003-4-3-207 . ISSN   1465-6906. PMC   153452 . PMID   12620097.
  28. ↑ Yang, Kefan; Coburger, Ina; Langner, Johanna M.; Peter, Nicole; Hoshi, Toshinori; Schönherr, Roland; Heinemann, Stefan H. (2019). "Modulation of K+ channel N-type inactivation by sulfhydration through hydrogen sulfide and polysulfides". Pflügers Archiv - European Journal of Physiology. 471 (4): 557–571. doi:10.1007/s00424-018-2233-x. PMC   7086210 . PMID   30415410 . Retrieved 2018-11-22.
  29. ↑ Holmgren, M.; Jurman, M. E.; Yellen, G. (September 1996). "N-type inactivation and the S4-S5 region of the Shaker K+ channel". The Journal of General Physiology. 108 (3): 195–206. doi:10.1085/jgp.108.3.195. ISSN   0022-1295. PMC   2229322 . PMID   8882863.
  30. ↑ Bénitah, J. P.; Chen, Z.; Balser, J. R.; Tomaselli, G. F.; Marbán, E. (1999-03-01). "Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation". The Journal of Neuroscience. 19 (5): 1577–1585. doi:10.1523/JNEUROSCI.19-05-01577.1999. ISSN   0270-6474. PMC   6782169 . PMID   10024345.
  31. ↑ Bähring, Robert; Covarrubias, Manuel (2011-01-28). "Mechanisms of closed-state inactivation in voltage-gated ion channels". The Journal of Physiology. 589 (3): 461–479. doi:10.1113/jphysiol.2010.191965. ISSN   0022-3751. PMC   3055536 . PMID   21098008.
  32. ↑ Kuo, Chung-Chin (1997-05-15). "Deactivation Retards Recovery from Inactivation in Shaker K+ Channels". The Journal of Neuroscience. 17 (10): 3436–3444. doi:10.1523/JNEUROSCI.17-10-03436.1997. ISSN   0270-6474. PMC   6573675 . PMID   9133369.
  33. ↑ Fowler, Philip W.; Sansom, Mark S. P. (2013-05-21). "The pore of voltage-gated potassium ion channels is strained when closed". Nature Communications. 4 (1): 1872. Bibcode:2013NatCo...4.1872F. doi:10.1038/ncomms2858. ISSN   2041-1723. PMC   3674235 . PMID   23695666.
  34. 1 2 Kamiya, Koki; Osaki, Toshihisa; Nakao, Kenji; Kawano, Ryuji; Fujii, Satoshi; Misawa, Nobuo; Hayakawa, Masatoshi; Takeuchi, Shoji (2018-11-30). "Electrophysiological measurement of ion channels on plasma/organelle membranes using an on-chip lipid bilayer system". Scientific Reports. 8 (1): 17498. Bibcode:2018NatSR...817498K. doi:10.1038/s41598-018-35316-4. ISSN   2045-2322. PMC   6269590 . PMID   30504856.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.