Kv1.3

Description: potassium voltage-gated channel, shaker-related subfamily, member 3
Gene: Kcna3
Alias: Kv1.3, kcna3

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Introduction

Kv1.3 (also known as MK3; HGK5; HLK3; PCN3; HPCN3; KV1.3; HUKIII), encoded by the gene KCNA3, is a member of the potassium voltage-gated channel subfamily A. Kv1.2 plays an essential role in T cell proliferation and activation. Kv1.3 channels are expressed in in various tissues and cell types including brain, vascular smooth muscle cells and leucocytes. Malfunction of Kv1.3 can alter the immune response, elicit neurotoxic effects or impact on cancer growth.[2002][1525]

Experimental data

Rat Kv1.3 gene in CHO host cells datasheet
Click for details 15 °C show 103 cells	Click for details 25 °C show 231 cells	Click for details 35 °C show 179 cells

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Gene

This gene appears to be intronless and is clustered together with KCNA2 and KCNA10 genes on chromosome 1.

Species	NCBI gene ID	Chromosome	Position
Human	3738	1	21380
Mouse	16491	3	1967
Rat	29731	2	1577

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_002232.5	2476
Mouse	NM_008418.2	1968
Rat	NM_019270.3	1578

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	P22001	575
Mouse	P16390	528
Rat	P15384	525

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NR_109846.1

6456

transcript variant 3

NR_109845.2

6355

transcript variant 2

NM_002232.5

2476

NP_002223.3

575

transcript variant 1

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Post-Translational Modifications

PTM

Position

Type

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Structure

Visual Representation of Kv1.3 Structure
Methodology for visual representation of structure available here

Voltage-gated K+ channels (Kv) are tetrameric molecules with six putative a-helical transmembrane segments (TM) linked by extra- and intracellular loops: the fifth and the sixth (S5-S6) TM’s and the connecting extracellular loop line the pore region and make up the conducting pore, whereas the first four (S1-S4) TM’s are thought to scaffold the activation gate of these channels [580].

High Resolution Crystallography

Using a high resolution crystal structure of Kv1.3, we see that Kv1.3-T1(51–155) is very similar to the known structures of the T1 domains derived from Aplysia Kv1.1 and rat Kv1.2. Ribbon-type representations of the tetramer are shown in Fig. 1a, b. The monomer consists of an N-terminal b-strand rich domain and a C-terminal a- helical domain [1538]

The most remarkable difference to the already published T1 domain structures is the occurrence of more than one side chain conformation for the residues Val55, Ile56, Leu77, Arg86, Tyr109, Arg116, Ser129, Glu140, Met142, and Arg146 [1538]

[1662]

Another difference to known structures is the slight but significant rotational displacement of the individual monomers in the tetrameric arrangement of the human Kv1.3 T1 domain. Such a rotational rearrangement in the T1 domain has been hypothesized to explain voltage- dependent gating rearrangement in the intracellular T1–T1 interfaces of Kv4 potassium channels observed through cysteine accessibility studies [1538]

Kv1.3 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	5329.77	source
Mouse	4881.28	source
Rat	4638.50	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Kv channels open on membrane depolarization, then get into a non-conducting, inactivated state. The activation of Kv channels is thought to be a conformational change initiated in the first four segments of the channel protein, while inactivation can occur by two mechanisms, called N-type and C-type [[581]] (/references/581).%3C%2Fp%3E%0A%0A%3Ch3%3ESingle%20Channel%20Current%3C%2Fh3%3E%0A%0A%3Cp%3EThe%20single%20channel%20conductance%20of%20Kv1.3%20is%2013%20pS,%20and%20the%20voltage%20required%20for%20activation%20is%20%E2%88%9235%20mV%20%3Ca%20href="/references/1525">[1525]

PK antagonists speed up inactivation of Kv1.3 current

To clarify the role of protein kinases in the regulation of Kv1.3 channels segregated into the IS we applied H89, GF109203X (GF), and damnacanthal (DAM), inhibitors of PKA (Kd ≈ 50 nM), PKC (Kd ≈ 14 nM), and p56lck (Kd = 17 and 620 nM), respectively. It was reported previously that these compounds have direct blocking effect on ion channels: H89 blocks Kv1.3 with an IC50 of 1.7 μM [1528]

Kv1.3 Kinetics Graph

[1531]

Kv1.3 currents (black) exhibited a fast activation and then a slow inactivation, evoked by 1 s depolarizing voltage steps ranging from −70 to +50 mV in 15 mV increments from a 90 s holding potential of −90 mV to remove the possible inactivation. [1532]

Kv1.3 Kinetics in CHO cells

The cDNA for Kv1.3 and Kv3.1 was subcloned into the PJB20 and pRc/CMV expression vector (Invitrogen). Kv1.3 currents exhibited characteristics typical of a delayed rectifier potassium channel when expressed in CHO cells. The apparent time course of inactivation was slow, with a time constant of about 150 msec [1790]

Kv1.3 currents recorded in Xenopus oocytes modulation by VP

Tracings were recorded in Xenopus oocytes injected with cRNA encoding Kv1.3 after 2 s of depolarizing pulses of -80 to +50 mV in 10 mV steps at a holding potential of -100mV. The coexpression of parvovirus B19 capsid protein VP1 significantly decreased K+ currents.[1988]

Kv1.3 steady-state activation in HEK 293T cells and blocking by Ctri9577

The steady-state activation of Kv1.3 channels was measured with a one-pulse protocol in HEK 293 cells. 200 ms voltage pulses were applied from -80 mV to 0 mV in 5 mV steps using a holding potential of -80 mV. The blocking process of the scorpion toxin Ctri9577 was shown not to be voltage -dependend for Kv1.3 channels.[1998]

Kv1.3 currents measured in Xenopus oocytes and enhancment by Klotho

K+ currents were measured in Xenopus oocytes injected with cRNA for KCNA3. Human Klotho protein significantly enhanced the Kv1.3 currents as well as the abundance of Kv1.3 expression.[1997]

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Biophysics

Kinetic Model

A simple sequential model for simultaneously simulating the whole kinetics of Kv1.3 currents including activation, deactivation, steady-state inactivation and recovery

HODGKIN/HUXLEY MODEL

Kinetic parameters of Kv1.3 gating changes in T cells in IS. The same protocols were applied to study kinetic and steady-state parameters of activation and inactivation. Normalized current traces demonstrate the activation of Kv1.3 current in stand alone cell and a cell engaged in IS. The activation for cells in IS could also be fitted according to n4 model by Hodgkin and Huxley (for these cells τa,c = 1.56 ms, τa,IS = 2.28 ms) [1528]

Model Kv1.3 (ID=38)

Animal	rat
CellType	Oocyte
Age	0 Days
Temperature	0.0°C
Reversal	-65.0 mV
Ion	K +
Ligand ion
Reference	[273] J P Adelman et. al; J. Immunol. 1990 Jun 15
mpower	1.0
m Inf	1.0000/(1+ exp((v - -14.1000)/-10.3000))
m Tau	(-0.2840 * v) + 19.1600 If v lt 50
m Tau	5 If v gteq 50
hpower	1.0
h Inf	1.0000/(1+ exp((v - -33.0000)/3.7000))
h Tau	(-13.7600 * v) + 1162.4000 If v lt 80
h Tau	60 If v gteq 80

MOD - xml - channelML

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Expression and Distribution

In Rhesus Macaque T-cells, the Kv1.3 expression pattern is similar to that in human T-cells [116].

While Kv1.3 channels are found in all T and B cell subsets in the resting state, their expression is markedly upregulated in activated effector memory T cells (TEMs) and Ig class-switched memory B cells from ~250 to ~1500 channels per cell [577],[578].

Kv1.3 immunoreactivity was found in the cerebellum, olfactory bulb, hippocampus, and cerebral cortex, particularly in frontal cortex. In coronal sections of the brainstem, prominent Kv1.3 immunoreactivity was found bilaterally in the MNTB, a nucleus that plays a key role in circuits that detect the localization of sounds in the azimuth. Lower levels of Kv1.3 were also detected in several other auditory brainstem nuclei [374]

Kv1.3 is also present in the central nervous system, kidney, liver, skeletal muscle, platelets, macrophages, testis, and osteoclasts [1530]

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CNS Sub-cellular Distribution

DENDRITIC CELLS

Potassium Channels Kv1.3 and Kv1.5 Are Expressed on Blood-Derived Dendritic Cells in the Central Nervous System [1703]

LYMPHOCYTES

To determine the cellular localization of Kv1.3, transmission electron microscopy studies were performed on freshly isolated peripheral human blood lymphocytes. These experiments surprisingly demonstrated the presence of the channel protein in mitochondria and confirmed the previously defined localization of Kv1.3 in the plasma membrane and in intracellular vesicles, most likely of the endoplasmic reticulum [1533]

Mitral cells

Kv1.3 expression in mitral cells of the olfactory bulb was shown to be involved in the mediation of glucose-sensitivity in these projection neurons [1944]

Nuclear distribution in cancer and neural tissue

Kv1.3 channels are primarily localized in the nucleus of several types of cells in cancer and in brain tissue. This nuclear distribution of Kv1.3 may be associated with gene regulation activity of Sp1[1980]

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Function

Regulates membrane potential in T cells

Kv1.3 regulates membrane potential and Ca2+ signaling in human T cells, and its expression is increased 4- to 5-fold in activated CD4+ and CD8+ TEM/TEMRA cells [1530]

Regulates physiological functions

Voltage-gated potassium channels (Kv) regulate several physiological functions of lymphocytes including membrane potassium permeability, calcium influx, cytokine production, clonal expansion and cell death [573], [574], [575], [576].

Acute Coronary Syndrome

Majority of patients with acute coronary syndrome have increased Kv1.3 activity in CD4+CD28null cells in peripheral blood and that the pro-inflammatory and cytotoxic activities of these cells can be reduced by Kv1.3 inhibitors [1529]

Autoimmune Disorders

The two major K+ channels that are expressed in lymphocytes, Kv1.3 and KCa3.1, are promising targets for the treatment of autoimmune disorders. Previous studies have described protective effects of Kv1.3 inhibitors or gene deletion on multiple sclerosis, type 1 diabetes, rheumatoid arthritis, psoriasis, and rapidly progressive glomerulonephritis. Moreover, KCa3.1 is related to acute immune responses and Kv1.3 is related to chronic immune responses, the combined administration with Kv1.3 and KCa3.1 inhibitors is likely to enhance their effects in autoimmune disorders or graft rejection [1700]

Cancers

The expression and relationship of Kv1.3 ion channel on several types of cancers (breast, prostate, muscle sarcoma, gliomas, leukemias and blood cancers) has been studied substantially [1525] Expression of Kv1.3 channels in colorectal cancers may point at an involvment of this channel-type in their formation [1986] Kv1.3channels also exhibited high expression levels in human osteosarcoma and were shown to promote their growth. This may indicate Kv1.3 channels as putative therapeutic targets [2004] Expression of Kv1.1 and Kv1.3 was shown to sensitize tumour cells of various origins to cytotoxins [1899] KCNA3 was reported as an efficient marker gene for parathyroid carcinoma [2006]

Integrin Signalling

In nonneuronal cells, the Kv1.3 channel forms a tight physical link with b-integrins, and the activity of the channel has been found to regulate integrin signaling and cell proliferation as well as the killing of neurons by microglia [374]

Diabetes

Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats [1530]

Cell Death

Examination of Kv1.3-deficient mice led to the discovery that Kv1.3, which seems to be abundantly expressed in brown and white fat, regulates energy homeostasis and body weight. Kv1.3 might therefore exert its regulatory effect on the basal metabolic rate directly in the mitochondria. Further finding that mitochondria contain Kv1.3 may also provide a plausible explanation for the fact that in actinomycin D-induced cell death mitochondria-associated events required expression of Kv1.3 [1533]

MS

The expression pattern revealed not only Kv1.3+ T cells in the perivenular infiltrate but also high expression in the parenchyma of demyelinated MS lesions and both normal appearing gray and white matter. This provides further rationale for the use of specific Kv1.3 antagonists in MS [1533]

Regulates Insulin

Kv1.3 also found to regulate Insulin in the periphery [1538]

Inflammation-mediated neurological disorders

Kv1.3 is involved microglia-mediated neurotoxic activity in HIV-1-infected brains, pointing at Kv1.3 inhibitors as novel therapeutics for inflammation-mediated neurological disorders [1945]

Regulation of cortical interneuron density

Expression of Kv1.3 channels is linked to the density of cortical interneuron types. KCNA null mice displayed an increase in the number of parvalbumin (PV) cells and a decrease in the number of calbindin (CB), calretinin (CR), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and somatostatin (SOM)expressing interneurons, as well as an overall reduction of cortical thickness [1946]

Kv1.3 and leukocyte activity

Kv1.3 channels were shown to have a modulatory effect on the cholesterol metabolism in macrophages. Specific Kv1.3 blockade may therefore constitute a novel strategy of therapeutic intervention in this metabolic process [1952] Kv1.3 blockade was also shown to enhance the phagocytic function in RAW264.7 macrophages [1971]

Blockade of Kv1.3 inhibited CD8+ T cell proliferation, secretion of GrB, and ability to kill neuron progenitors [1954] Proinflammatory cytokine secretion was also reduced in T(EM) cells by inhibition of hKv1.3 with curcumin [1953] Accordingly, B lymphocyte proliferation and Ly-6Chi monocyte chemotaxis were promoted by the opening of KCa3.1 and Kv1.3 channels [1974]Also PSD-95 targeting of Kv1.3 to the immunological synapse, during T-cell activation, implies a role of Kv1.3 channels in the activation process [1958] The effects of Kv1.3 inhibition on leukocytes make Kv1.3 a potential target for immunosuppression during allotransplantation [1956]

Kv1.3 in Immune-mediated disorders

Kv1.3 blockers ameliorate allergic contact dermatitis by suppressing effector memory T cells in a rat model [1960] Blocking KV1.3 channels was shown to inhibit Th2 lymphocyte function and to treat a rat model of asthma [1526] KV1.3 expression in T cells correlated with pro-inflammatory cytokines in ulcerative colitis [1963] Kv1.3 inhibition in lymphocytes was shown to have a therapeutic potential in acute ischemic stroke [1965] The effectivness of Kv1.3 inhibition in treating psoriatic disease was demostrated by PAP-1 inhibition of Kv1.3 in the mouse model [1966] Functional evidence has been provided for the role of Kv1.3 channels in lymphocytes of spontaneously hypertensive rats during aging [1970] Also, in patients with hypertension an increase of Kv1.3 and KCa3.1 expression in T cells has been reported [1973] Kv1.3 and IKCa1 channel inhibition alters calcium influx in human peripheral T lymphocytes in rheumatoid arthritis [1950]

Secretory pathway of Kv1.3

According to a mutation study the pore loop residues of Kv1.3 form a canonical α-helix within the monomer during the early biogenesis [1977] The posttranslational modification of Kv1.3 is localized to the cis-Golgi while that of Kv1.6 is localized to the endoplasmic reticulum in astrocytes. [1978] Kv1.3 contains an alternative ER exit motif involved in recruiting the channel into COPII vesicles by Sec24a [1981] A further, previously unrecognized motif of Kv channels is essential for their expression on the cell surface [1976] Membrane motility of Kv1.3 channels is then regulated by actin dynamics and mediated by the SH3 motif of Kv1.3 and cortactin [1979] Kv1.3 channels may undergo endocytosis initiated by EGF-dependent ERK1/2 activation and subsequent phosphorilation of threonine residues [1982]

Kv1.3-induced proliferation

Kv1.3-induced cell proliferation involves accessibility of C-terminus(Y447) and phosphorylation via MEK/ERK [1983]

Atherosclerosis

Changes in Kv1.3 channel gating behaviour in T lymphocytes have been associated with atherosclerosis [1999] Kv1.3 channels activity may also contribute to atherosclerosis by stimulating macrophage migration through the activation of ERK [2000] The importance of Kv1.3 in atherosclerosis is further supported by the finding that the Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model [1529]

Neurotoxicity

Kaliotoxin (KTX) is a neurotoxin purified from the androctonus scorpion venom causing neuropathophysiological and immuno-inflammatory effects. Kv1.1 and Kv1.3 channels are targeted by KTX-binding in the CNS inducing severe modifications though the activation of immuno-inflammatory reactions [2001]Kv1.3 function was suggested to play a role in neurotoxic pathways. ShK-170 blockade of Kv1.3 ameliorates radiation-induced brain injury by suppression of microglial neurotoxicity [2002] Kv1.3 channel activity was also linked to methamphetamine-mediated microglial damage [2003]

Vascular smooth muscle cells

Kv1.3 channel blockers decrease proliferation, migration and hyperplasia of vascular smooth muscle cells (VSMCs), indicating a role of the channel in these processes. Kv1.3 channels were therefore suggested as as novel therapeutical targets in restenosis [2005] The involvement of Kv1.3 channels in the phenotypic modulation of human VSMCs highlights Kv1.3 as an alternative target to blocking mTOR [2007]

Neuron density

Deletion of the Kv1.3 alters mitral cell current properties contributing to a "Super-smeller" phenotype. An increase in mitral cell density was observed in these Kv1.3-null mice [2008]

Neuron differentiation and maturation

Kv1.3 channels may play a crucial role of in the regulation of neuroprogenitor cell differentiation and maturation. Blocking Kv1.3 with Psora-4 promoted neural differentiation and maturation [2010]

Pacemaking activity in SNc

Kv1.3 was identified as one of the subunits of voltage-gated ion channels in the substantia nigra pars compacta (SNc) that contribute to the somatodendritic delayed rectifier in dopaminergic neurons, others being Kv2.1, Kv3.2, Kv3.3, Kv4.3 [2009]

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Interaction

PAP-1

(5-(4-phenoxybutoxy)psoralen), PAP-1, is a synthetic derivate of the natural product 5-methoxypsoralen and exhibits a 23 to 125-fold selectivity for Kv1.3 over other members of the Kv1 family, effectively blocking Kv1.3 with an EC50 of 2 nM and a stoichiometry of 2 inhibitor molecules per channel [579].

MbCD and MbCD/C

Manipulation of membrane cholesterol oligosaccharide methyl-b-cyclodextrin (MbCD) and its cholesterol-saturated complex (MbCD/C) changed both the kinetic properties of Kv1.3 and steady-state parameters of activation by modifying lipid–protein interactions. [117]

Zn

Zn+2 ion concentration does not modulate Kv1.3 channel kinetics, although other Kv1 channels are affected. [118]

Leukocyte Kv channel Subunits effect Kv1.3

Leukocytes also express several regulatory subunits which may associate with Kv1.3 complexes to enhance diversity and modulate a wide variety of physiological activities. In fact, Kv1.3 channels are able to assemble with Kvβ subunits to form functional Kv channels. Kvβ subunits alter current amplitude and gating, confer rapid inactivation, and promote Kv surface expression. In addition, heterologous expression of Kv1.3 and Kv1.5 with Kvβ subunits in Xenopus oocytes and mammalian cells, dramatically modifies the rate of inactivation and the K+ current density [1525]

Cluster at C-terminus

A Y479MVIEE484 cluster at the C-terminus of the channel was found responsible for efficient Kv1.3 forward trafficking. This domain is highly conserved in neuronal isoforms of the Kv1 family. The di-acidic (E483/484) motif within the Y479MVIEE484 cluster was the main determinant for Kv1.3 surface expression [1976]

Kv1.3 associates with Kv1.5

Kv1.3 associates with Kv1.5, leading to biophysically and pharmacologically distinct channels. They also generate multiple heterotetramers with differential surface expression according to the subunit composition. FRET analysis and pharmacology confirm the presence of functional hybrid channels. Moreover, FRAP analysis revealed higher mobility for hybrid Kv1.3/Kv1.5 than Kv1.3 homotetramers, suggesting that heteromers target to distinct surface micro domains [1527]

Kv1.3 forms heteromeric channels

Kv1.3 subunit can form heteromeric channels with other Kv1 subfamily subunits. Among the subunits demon- strated to form heteromers with Kv1.3 in vivo are Kv.1.1, Kv1.2, and Kv1.6 [374]

Scorpion toxin ADWX-1 is a pore blocker of Kv1.3 channel without affecting its kinetics

Engineered scorpion toxin ADWX-1 is a potent specific inhibitor of Kv1.3. It has the highest affinity in ~pM to Kv1.3 channels. ADWX-1 blocked the Kv1.3 currents without changing the G-V curve and the time constants of activation and inactivation. This means that the inhibition by ADWX-1 only reduces the number of open channels without affecting the channel kinetics. This allows us to explore the Kv1.3 role in T cell by simply changing the number of Kv1.3 channels in applying with different ADWX-1 concentrations [1532]

Nystatin

The concentrations for nystatin and its structural analog, amphotericin B, required to produce half maximal inhibition (IC50) of the current were estimated to be about 3 and 60 microM, respectively. The effects of nystatin on the amplitude and inactivation of Kv1.3 currents were not voltage-dependent. In inside-out patches, tetraethylammonium (TEA) produced a rapid block of Kv1.3 currents upon the onset of a voltage pulse, while the inhibition by nystatin developed slowly. When co-applied with TEA, nystatin potentiated the extent of the TEA-dependent block, and the kinetic effect of nystatin was slowed by TEA. In summary, nystatin, a compound frequently used in perforated patch recordings to preserve intracellular dialyzable components, specifically inhibited the potassium channel Kv1.3 at concentrations well below those required for perforation [1790]

Sphingomyelinase

The sphingomyelinase enzyme was shown to stimulate native K(v)1.3 channels in nonexcitable human T lymphocytes [1947]

Immunorepressants associated with Kv1.3 modulation

A mutation of the ShK peptide can enhance its specificity for Kv1.3 and act as selective blocker in the treatment of autoimmune diseases [1948]
Dihydropyridine Ca(2+) channel blockers, such as nifedipine and benidipine, exert inhibitory effects on thymocyte Kv1.3-channel currents [1951]
Curcumin was shown to inhibit proinflammatory cytokine secretion of T(EM) cells by blocking of hKv1.3 [1953]
Clofazimine, Psora-4 and PAP-1 present a therapeutic potential for treatment of leukemia due to their inhibitory effects on Kv1.3 channels [1955]
Clarithromycin exerts inhibitory effects on thymocyte Kv1.3-channel currents [1957]
18β-Glycyrrhetinic acid potently inhibits Kv1.3 channels and T cell activation in Jurkat T cells [1959]
NMDAR antagonists likely exert their immunosuppressant effect on T cells through the mediation by Kv1.3 and KCa3.1 channels [1961]
The scorpion toxin analogue HsTX1, a potent and selective Kv1.3 blocker, may be a potential therapeutic for autoimmune diseases [1962]
Statins modulate thymocytes via the inhibition of Kv1.3-channels [1964]
PAP-1 inhibition of Kv1.3 was shown to be effective in psoriatic disease in the mouse model [1966]
Acacetin blocking of the Kv1.3 channel inhibited human T cell activation [1967]
Xanthohumol and Isoxanthohumol inhibition of Kv1.3 channels was associated with antiproliferative and proapoptotic effect in lymphocytes [1968]
Cortisone and hydrocortisone are supposed to exert their immunerepressive effects in part by inhibition of Kv1.3 currents via a non-genomic mechanism [1969]
Diltiazem and verapamil, known as Ca channel blockers, exert inhibitory effects on Kv1.3 in lymphocytes [1972]
Telmisartan blocked the increased Kv1.3 and KCa3.1 expression in T cells of patients with hypertension [1973]
Lovastatin exerts immunodulatory properties by blocking of Kv1.3 channels [1975]

EV37 scorpion toxins

Ev37 scorpion toxins elicit cytolytic effects by interaction with Kv1.3 channels. Since they are not effectively blocking Kv1.1 and Kv1.2 channels, Ev37 peptides have been suggested as a new type of selective Kv1.3 channel blockers [1985]

MMP-23 prodomain

The prodomain of the matrix metalloprotease MMP-23 was shown to suppress KV1.3 by intracellular trapping. A proccess not obeserved for KV1.2 channels. The overlap of expression with colorectal cancers indicates a possible involvment of the MMP-23 prodomain and Kv1.3 in this pathology [1986]

Hetlaxin

Hetlaxin, a scorpion toxin from the venom of Heterometrus laoticus, interacts with voltage-gated potassium channel Kv1.3. [1987]

Capsid protein VP1

Parvovirus B19 capsid protein VP1 inhibits Kv1.3 and Kv1.5 channels in host cells. This inhibition was shown to be linked to PLA-dependent formation of lysophosphatidylcholine [1988]

Human β-defensin 2

human β-defensin 2 (hBD2) was reported as a novel modulator of Kv1.3 channels. The hBD2 modulation of Kv1.3 channels involves its interaction with a novel receptor site at the S1-S2 linker. hBD2 positively shifts the conductance-voltage curve of hKv1.3 channels by 10.5 mV and increases its activation time [1989]

BF9 peptide

BF9 is a snake peptide that exhibits a unique bifunctionality of Kv1.3 channel and serine protease inhibiting properties. It is therefore the first reported Kunitz-type snake toxin with protease and potassium channel inhibiting properties [1990]

Loureirin B

Loureirin B a component of the herbal medicine Sanguis draxonis is a blocker of Kv1.3 channels. Its interacting with amino acid residues in the Kv1.3 selectivity filter [1991]