KCNB1

The general structure of all potassium channels contain a centered pore composed of alpha subunits with a pore loop expressed by a segment of conserved DNA, T/SxxTxGxG. This general sequence comprises the selectivity of the potassium channel. Depending on the channel, the alpha subunits are constructed in either a homo- or hetero-association, creating a 4-subunit selectivity pore or a 2-subunit pore, each with accessory beta subunits attached intracellularly. Also on the cytoplasmic side are the N- and C- termini, which play a crucial role in activating and deactivating KCNB1 channels. This pore creates the main opening of the channel where potassium ions flow through.{{cite journal | vauthors = Wray D | title = The roles of intracellular regions in the activation of voltage-dependent potassium channels| journal = European Biophysics Journal | volume = 33 | issue = 3 | pages = 194–200 | date = May 2004 | pmid = 14608450 | doi = 10.1007/s00249-003-0363-2 | s2cid = 7990617}}

The type of pore domain (number of subunits) determines if the channel has the typical 6 transmembrane (protein) spanning regions, or the less dominant inward rectifier type of only 2 regions. KCNB1 has 6TM labeled S1-S6, each with a tetrameric structure. S5 and S6 create the p-loop, while S4 is the location of the voltage sensor. S4, along with S2 and S3 create the ‘activating’ portions of the delayed rectifier channel. The heteromeric complexes that contain the distinct pore are electrically inactive or non-conducting, but unlike other potassium families, the pore of the KCNB1 group has numerous phosphorylation sites allowing kinase activity. Maturing KCNB1 channels develop these phosphorylation sites within the channel pore, but lack a glycosylation stage in the N-terminus.

Specifically, the KCNB1 delayed rectifier channel conducts a potassium current (K+). This mediates high frequency firing due to the phosphorylation sites located within the channel via kinases and a major calcium influx typical of all neurons.{{cite journal | vauthors = Patel R, Sesti F | title = Oxidation of ion channels in the aging nervous system | journal = Brain Research | volume = 1639 | pages = 174–85 | date = May 2016 | pmid = 26947620 | doi = 10.1016/j.brainres.2016.02.046 | url = https://zenodo.org/record/895322 | doi-access = free }}

The kinetics surrounding the activation and deactivation of the KCNB1 channel is relatively unknown, and has been under considerable study. Three of the six transmembrane regions, S2, S3 and S4, contribute to the activation phase of the channel. Upon depolarization, the S4 region, which is positively charged, is moved in response to the subsequent positive charge of the depolarization. As a result of S4 movement, the negatively charged regions of S2 and S3 appear to move as well. The movement of these regions causes an opening of the channel gate within regions of S5 and S6.{{cite journal | vauthors = Wray D | title = Intracellular regions of potassium channels: Kv2.1 and heag| journal = European Biophysics Journal | volume = 38 | issue = 3 | pages = 285–92 | date = March 2009 | pmid = 18607586 | doi = 10.1007/s00249-008-0354-4 | s2cid = 37362059}} The intracellular regions of the C and N-terminus also play a crucial role in the activation kinetics of the channel. The two termini interact with one other, as the C-terminus folds around the N-terminus during channel activation. The relative movement between the N- and C- termini greatly aids in producing a conformational change of the channel necessary for channel opening. This interaction between these intracellular regions is believed to be linked with membrane-spanning regions of S1 and S6, and thus aid in the movement of S2, S3, and S4 in opening the channel. Studies on selective mutations knocking out these intracellular termini have been shown to produce larger reductions in speed and probability of channel opening, which indicates their importance in channel activation.

Voltage-gated potassium (K_v) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Delayed rectifier potassium channels’ most prevalent role is in the falling phase of physiological action potentials. KCNB1 rectifiers are also important in forming the cardiac beat and rate synchronicity that exists within the heart, and the lysis of target molecules in the immune response. These channels can also act as effectors in downstream signaling in G-protein coupled receptor transduction. KCNB1's regulation and propagation of current provides a means for regulatory control over several physiological functions. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and apoptosis.

Voltage-gated potassium channels are essential in regulating neuronal membrane potential, and in contributing to action potential production and firing.{{cite journal | vauthors = Sesti F | title = Oxidation of K(+) Channels in Aging and Neurodegeneration | journal = Aging and Disease | volume = 7 | issue = 2 | pages = 130–5 | date = March 2016 | pmid = 27114846 | pmc = 4809605 | doi = 10.14336/AD.2015.0901 }} In mammalian CNS neurons, KCNB1 is a predominant delayed rectifier potassium current that regulates neuronal excitability, action potential duration, and tonic spiking. This is necessary when it comes to proper neurotransmitter release, as such release is dependent on membrane potential. In mouse cardiomyocytes, KCNB1 channel is the molecular substrate of major repolarization current I_K-slow2. Transgenic mice, expressing a dominant-negative isoform of KCNB1, exhibit markedly prolonged action potentials and demonstrate arrhythmia.{{cite journal | vauthors = Murakoshi H, Trimmer JS | title = Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons | journal = The Journal of Neuroscience | volume = 19 | issue = 5 | pages = 1728–35 | date = March 1999 | pmid = 10024359 | pmc = 6782166 | url = | doi = 10.1523/JNEUROSCI.19-05-01728.1999 }} KCNB1 also contributes to the function and regulation of smooth muscle fibers. Human studies on pulmonary arteries have shown that normal, physiological inhibition of KCNB1 current aids vasoconstriction of arteries.{{cite journal | vauthors = Joseph BK, Thakali KM, Moore CL, Rhee SW | title = Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches | journal = Pharmacological Research | volume = 70 | issue = 1 | pages = 126–38 | date = April 2013 | pmid = 23376354 | pmc = 3607210 | doi = 10.1016/j.phrs.2013.01.008 }} In human pancreatic ß cells, KCNB1, which mediates potassium efflux, produces a downstroke of the action potential in the cell.{{cite journal | vauthors = Yang SN, Shi Y, Yang G, Li Y, Yu J, Berggren PO | title = Ionic mechanisms in pancreatic β cell signaling | journal = Cellular and Molecular Life Sciences | volume = 71 | issue = 21 | pages = 4149–77 | date = November 2014 | pmid = 25052376 | doi = 10.1007/s00018-014-1680-6 | s2cid = 9830297 | pmc = 11113777 }} In effect, this behavior halts insulin secretion, as its activation decreases the Ca_v channel-mediated calcium influx that is necessary for insulin exocytosis. KCNB1 has also been found to promote apoptosis within neuronal cells. It is currently believed that KCNB1-induced apoptosis occurs in response to an increase in reactive oxygen species (ROS) that results either from acute oxidation or as a consequence of other cellular stresses.

KCNB1 conductance is regulated primarily by oligomerization and phosphorylation. Additional forms of regulation include SUMOylation and acetylation, although the direct effect of these modifications is still under investigation. KCNB1 consensus sites in the N-terminus are not subject to glycosylation.

Many proteins undergo phosphorylation, or the addition of phosphate groups to amino acids subunits. Phosphorylation is modulated by kinases, which add phosphate groups, and phosphatases, which remove phosphate groups. In its phosphorylated state, KCNB1 is a poor conductor of current. There are 16 phosphorylation sites that are subject to the activity of kinases, such as cyclin-dependent kinase 5 and AMP-activated protein kinase. These sites are reversibly regulated by phosphatases such as, phosphatase calcineurin. Under periods of high electrical activity, depolarization of the neuron increases calcium influx and triggers phosphatase activity. Under resting conditions, KCNB1 tends to be phosphorylated. Phosphorylation raises the threshold voltage requirement for activation and allows microdomains to bind the channel, preventing KCNB1 from entering the plasma membrane. Microdomains localize KCNB1 in dendrites in cell bodies of hippocampal and cortical neurons. Conductance associated with de-phosphorylation of this channel acts to decrease or end periods high excitability. However, this relationship is not static and is cell dependent. The role of phosphorylation can be affected by reactive oxygen species (ROS) that increase during oxidative stress. ROS act to increase the levels of zinc (Zn²⁺⁾ and calcium (Ca²⁺⁾ intracellularly that act with protein kinases to phosphorylate certain sites on KCNB1. This phosphorylation increases the insertion of KCNB1 into the membrane and elevates conductance. Under these conditions the interaction with SNARE protein syntaxin, is enhanced. This surge of KCNB1 current induces activation of a pro-apoptotic pathway, DNA fragmentation, and caspase activation.{{cite journal | vauthors = Shah NH, Aizenman E | title = Voltage-gated potassium channels at the crossroads of neuronal function, ischemic tolerance, and neurodegeneration | journal = Translational Stroke Research | volume = 5 | issue = 1 | pages = 38–58 | date = February 2014 | pmid = 24323720 | pmc = 3946373 | doi = 10.1007/s12975-013-0297-7 }}

Another proposed mechanism for regulation of apoptosis is oligomerization, or the process of forming multi-protein complexes held together through disulfide bonds. Under oxidative stress, reactive oxygen species (ROS) form and act to regulate KCNB1 through oxidation. Increase in oxygen radicals directly causes formation of KCNB1 oligomers that then accumulate in the plasma membrane and initially decrease current flow.{{cite journal |vauthors=Wu X, Hernandez-Enriquez B, Banas M, Xu R, Sesti F |title=Molecular mechanisms underlying the apoptotic effect of KCNB1 K+ channel oxidation.|journal=J Biol Chem|date=2013|volume=288|issue=6|pages=4128–4134|doi=10.1074/jbc.M112.440933|pmid=23275378|pmc=3567663|doi-access=free}}{{cite journal |vauthors=Cotella D, Hernandez B, Wu X, Li R, Pan Z, Leveille J, Link CD, Oddo S, Sesti F |title=Toxic role of K+ channel oxidation in mammalian brain|journal=J. Neurosci.|date=2012|volume=32|issue=12|pages=4133–4144|doi=10.1523/JNEUROSCI.6153-11.2012|pmid=22442077|pmc=6621216}} Oligomer activation of c-Src and JNK kinases induces the initial pro-apoptotic signal, which is coupled to KCNB1 current. This further promotes the apoptosis pathway.{{cite journal |vauthors=Yu W, Gowda M, Singh S, Sesti F |title=Oxidation of KCNB1 potassium channels triggers apoptotic integrin signaling in the brain.|journal=Cell Death Dis.|date=2017|volume=8|issue=4|page=e2737|doi=10.1038/cddis.2017.160|pmid=28383553|pmc=5477583}} KCNB1 oligomers have been detected in the post mortem human hippocampus {{cite journal |vauthors=Wei Y, Shih R, Sesti F |title=Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer's disease |journal=Cell Death Dis. |date=2018 |volume=9 |issue=820 |pages=820 |doi=10.1038/s41419-018-0886-1|pmid=30050035 |pmc=6062629 }}

Potassium delayed rectifiers have been implicated in many pharmacological uses in the investigation of biological toxins for drug development. A main component to many of the toxins with negative effects on delayed rectifiers contain cystine inhibitors that are arranged around disulfide bond formations. Many of these toxins originate from species of tarantulas. G. spatulata produces the hanatoxin, which was the first drug to be manipulated to interact with KCNB1 receptors by inhibiting the activation of most potassium voltage-gated channels. Other toxins, such as stromatoxin, heteroscordratoxin, and guangxitoxin, target the selectivity of voltage KCNB1 rectifiers, by either lowering potassium binding affinity or increasing the binding rate of potassium. This can lead to excitotoxicity, or overstimulation of postsynaptic neurons. In nature, the prey of tarantula that are injected with these endogenous toxins induces this excitotoxic effect, producing paralysis for easy capture. Physiologically, these venoms work on KCNB1 rectifier affinity by altering the channels’ voltage sensor, making it more or less sensitive to extracellular potassium concentrations.{{cite journal | vauthors = Swartz KJ | title = Tarantula toxins interacting with voltage sensors in potassium channels | journal = Toxicon | volume = 49 | issue = 2 | pages = 213–30 | date = February 2007 | pmid = 17097703 | pmc = 1839852 | doi = 10.1016/j.toxicon.2006.09.024 | bibcode = 2007Txcn...49..213S }} KCNB1 is also susceptible to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), which completely block all channel activity. TEA also works on calcium-activated potassium channels, furthering its inhibitory effects on neurons and skeletal muscle. Some isoforms of TEA are beneficial for patients with severe Alzheimer's, as blocking KCNB1 channels reduces the amount of neuronal apoptosis, thereby slowing the rate of dementia.{{cite journal | vauthors = Quinn CC, Begenisich T | title = Pharmacology and surface electrostatics of the K channel outer pore vestibule | journal = The Journal of Membrane Biology | volume = 212 | issue = 1 | pages = 51–60 | date = 2017-04-12 | pmid = 17206516 | pmc = 1784061 | doi = 10.1007/s00232-006-0039-9 }} This has been attributed to the oxidative properties of the channel by ROS.

Oxidative damage is widely considered to play a role in neurodegenerative disorders, including Alzheimer's disease. Such oxidative stress alters the redox sensitivity of the Kv2.1 delayed rectifier, resulting in the modulation of the channel. In vitro studies and studies in animal models show that when KCNB1 is oxidized, it no longer conducts, leading to neurons becoming hyperpolarized and dying; oxidized KCNB1 also clusters in lipid rafts and cannot be internalized, which also leads to apoptosis. These alterations disrupt normal neuronal signaling and increase the likelihood of neurological diseases. Oxidized (oligomerized) KCNB1 channels are present in the hippocampi of old (Braak stage 1-2) and Alzheimer's disease (Braak stage 5) donors of either sexes {{cite journal | vauthors = Peers C, Boyle JP | title = Oxidative modulation of K+ channels in the central nervous system in neurodegenerative diseases and aging | journal = Antioxidants & Redox Signaling | volume = 22 | issue = 6 | pages = 505–21 | date = February 2015 | pmid = 25333910 | doi = 10.1089/ars.2014.6007 | url = http://eprints.whiterose.ac.uk/98726/8/accepted%20version.pdf }}

As indicated earlier, oxidative and nitrosative injurious stimuli also activate a cell death-inducing cascade that promotes to a zinc and calcium/clamodulin-dependent interaction between syntaxin and Kv2.1, leading to the pro-apoptotic insertion of additional potassium channels into the plasma membrane. These new population of channels aid in the loss of intracellular potassium, creating a permissive environment for protease and nuclease activation in injured neurons. Agents that interfere with the Kv2.1/syntaxin interaction are highly neuroprotective in acute ischemic injury models (stroke) {{cite journal | vauthors = Yeh CY, Bulas AM, Moutal A, Saloman JL, Hartnett KA, Anderson CT, Tzounopoulos T, Sun D, Khanna R, Aizenman E | title = Targeting a potassium channel/syntaxin interaction ameliorates cell death in ischemic stroke. | journal = Journal of Neuroscience | volume = 37 | issue = 23 | pages = 5648–5658 | date = June 2017 | pmid = 28483976 | pmc = 5469303 | doi = 10.1523/JNEUROSCI.3811-16.2017 }}

Increased probability of the channel remaining open can also potentially drive neurodegeneration. Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) may be driven by an overabundance of glutamate, which in turn can trigger increased calcium levels, which in turn can drive calcium-dependent dephosphorylation of KCNB1 channels, which increases probability of channel activation and current conductance. Enhanced KCNB1 current couples cell shrinkage associated with apoptosis and dendritic beading leading to diminished long term potentiation. These neuronal modifications may explain the atrophy of cell layer volume and late stage cell death observed in HAD disease.{{cite journal | vauthors = Keblesh J, Hu D, Xiong H | title = Voltage-gated potassium channels in human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorders | journal = Journal of Neuroimmune Pharmacology | volume = 4 | issue = 1 | pages = 60–70 | date = March 2009 | pmid = 18459047 | pmc = 3974578 | doi = 10.1007/s11481-008-9106-6 }}

Exploitation of this channel is advantageous in cancer cell survival as they have the ability to produce heme oxygenase-1, an enzyme with the ability to generate carbon monoxide (CO). Oncogenic cells benefit from producing CO due to the antagonizing effects of the KCNB1 channel. Inhibition of KCNB1 allows cancer proliferation without the apoptotic pathway preventing tumor formation. Although potassium channels are studied as a therapeutic target for cancer, this apoptotic regulation is dependent on cancer type, potassium channel type, expression levels, intracellular localization as well as regulation by pro- or anti-apoptotic factors.{{cite journal | vauthors = Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N | title = Ion channels in the regulation of apoptosis | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1848 | issue = 10 Pt B | pages = 2532–46 | date = October 2015 | pmid = 25450339 | doi = 10.1016/j.bbamem.2014.10.030 | series = Membrane Channels and Transporters in Cancers | doi-access = free }}

KCNB1 has been shown to interact with:

• KCNH1,{{cite journal | vauthors = Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ | title = Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 12 | pages = 7986–91 | date = June 2002 | pmid = 12060745 | pmc = 123007 | doi = 10.1073/pnas.122617999 | bibcode = 2002PNAS...99.7986O | doi-access = free }} and
• PTPRE.{{cite journal | vauthors = Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A | title = Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon | journal = The EMBO Journal | volume = 19 | issue = 15 | pages = 4036–45 | date = August 2000 | pmid = 10921884 | pmc = 306594 | doi = 10.1093/emboj/19.15.4036 }}

• Voltage-gated potassium channel
• Guangxitoxin

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Albrecht B, Lorra C, Stocker M, Pongs O | title = Cloning and characterization of a human delayed rectifier potassium channel gene | journal = Receptors & Channels | volume = 1 | issue = 2 | pages = 99–110 | year = 1994 | pmid = 8081723 }}
• {{cite journal | vauthors = Hugnot JP, Salinas M, Lesage F, Guillemare E, de Weille J, Heurteaux C, Mattéi MG, Lazdunski M | title = Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels | journal = The EMBO Journal | volume = 15 | issue = 13 | pages = 3322–31 | date = July 1996 | pmid = 8670833 | pmc = 451895 | doi = 10.1002/j.1460-2075.1996.tb00697.x}}
• {{cite journal | vauthors = Post MA, Kirsch GE, Brown AM | title = Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current | journal = FEBS Letters | volume = 399 | issue = 1–2 | pages = 177–82 | date = December 1996 | pmid = 8980147 | doi = 10.1016/S0014-5793(96)01316-6 | s2cid = 5691552 | doi-access = free | bibcode = 1996FEBSL.399..177P }}
• {{cite journal | vauthors = Patel AJ, Lazdunski M, Honoré E | title = Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes | journal = The EMBO Journal | volume = 16 | issue = 22 | pages = 6615–25 | date = November 1997 | pmid = 9362476 | pmc = 1170266 | doi = 10.1093/emboj/16.22.6615 }}
• {{cite journal | vauthors = Shepard AR, Rae JL | title = Electrically silent potassium channel subunits from human lens epithelium | journal = The American Journal of Physiology | volume = 277 | issue = 3 Pt 1 | pages = C412-24 | date = September 1999 | pmid = 10484328 | doi = 10.1152/ajpcell.1999.277.3.C412}}
• {{cite journal | vauthors = Zhu XR, Netzer R, Böhlke K, Liu Q, Pongs O | title = Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel | journal = Receptors & Channels | volume = 6 | issue = 5 | pages = 337–50 | year = 1999 | pmid = 10551266 }}
• {{cite journal | vauthors = Sano Y, Mochizuki S, Miyake A, Kitada C, Inamura K, Yokoi H, Nozawa K, Matsushime H, Furuichi K | title = Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K(+) channel Kv2.1 | journal = FEBS Letters | volume = 512 | issue = 1–3 | pages = 230–4 | date = February 2002 | pmid = 11852086 | doi = 10.1016/S0014-5793(02)02267-6 | s2cid = 83987133 | doi-access = free }}
• {{cite journal | vauthors = Kurata HT, Soon GS, Eldstrom JR, Lu GW, Steele DF, Fedida D | title = Amino-terminal determinants of U-type inactivation of voltage-gated K+ channels | journal = The Journal of Biological Chemistry | volume = 277 | issue = 32 | pages = 29045–53 | date = August 2002 | pmid = 12021261 | doi = 10.1074/jbc.M111470200 | doi-access = free }}
• {{cite journal | vauthors = MacDonald PE, Wang G, Tsuk S, Dodo C, Kang Y, Tang L, Wheeler MB, Cattral MS, Lakey JR, Salapatek AM, Lotan I, Gaisano HY | title = Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus | journal = Molecular Endocrinology | volume = 16 | issue = 11 | pages = 2452–61 | date = November 2002 | pmid = 12403834 | doi = 10.1210/me.2002-0058 | doi-access = free }}
• {{cite journal | vauthors = Ju M, Stevens L, Leadbitter E, Wray D | title = The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel | journal = The Journal of Biological Chemistry | volume = 278 | issue = 15 | pages = 12769–78 | date = April 2003 | pmid = 12560340 | doi = 10.1074/jbc.M212973200 | doi-access = free }}
• {{cite journal | vauthors = Tiran Z, Peretz A, Attali B, Elson A | title = Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase epsilon | journal = The Journal of Biological Chemistry | volume = 278 | issue = 19 | pages = 17509–14 | date = May 2003 | pmid = 12615930 | doi = 10.1074/jbc.M212766200 | doi-access = free }}
• {{cite journal | vauthors = Consiglio JF, Korn SJ | title = Influence of permeant ions on voltage sensor function in the Kv2.1 potassium channel | journal = The Journal of General Physiology | volume = 123 | issue = 4 | pages = 387–400 | date = April 2004 | pmid = 15024041 | pmc = 2217458 | doi = 10.1085/jgp.200308976 }}
• {{cite journal | vauthors = Thébaud B, Michelakis ED, Wu XC, Moudgil R, Kuzyk M, Dyck JR, Harry G, Hashimoto K, Haromy A, Rebeyka I, Archer SL | title = Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus | journal = Circulation | volume = 110 | issue = 11 | pages = 1372–9 | date = September 2004 | pmid = 15353504 | doi = 10.1161/01.CIR.0000141292.28616.65 | doi-access = free }}
• {{cite journal | vauthors = Kerschensteiner D, Soto F, Stocker M | title = Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 17 | pages = 6160–5 | date = April 2005 | pmid = 15827117 | pmc = 1087924 | doi = 10.1073/pnas.0500468102 | bibcode = 2005PNAS..102.6160K | doi-access = free }}

{{refend}}

• {{MeshName|Kv2.1+Potassium+Channel}}
• {{MeshName|KCNB1+protein,+human}}

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{{Ion channels|g3}}

Category:Ion channels