Two P domain potassium channels in GtoPdb v.2021.2

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two P domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below.

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Two-pore domain potassium channels (K2P) in GtoPdb v.2021.3

IUPHAR/BPS Guide to Pharmacology CITE ◽

10.2218/gtopdb/f79/2021.3 ◽

2021 ◽

Vol 2021 (3) ◽

Author(s):

Austin M. Baggetta ◽

Douglas A. Bayliss ◽

Gábor Czirják ◽

Péter Enyedi ◽

Steve A.N. Goldstein ◽

...

Keyword(s):

Single Channels ◽

Primary Sequence ◽

Α Subunit ◽

Voltage Range ◽

K Channels ◽

Structural And Functional Properties ◽

Conduction Pathway ◽

K2p Channels ◽

The Common ◽

Pore Domain

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two-pore domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below.

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Batrachotoxin-activated Na+ channels in planar lipid bilayers. Competition of tetrodotoxin block by Na+.

The Journal of General Physiology ◽

10.1085/jgp.84.5.665 ◽

1984 ◽

Vol 84 (5) ◽

pp. 665-686 ◽

Cited By ~ 87

Author(s):

E Moczydlowski ◽

S S Garber ◽

C Miller

Keyword(s):

Lipid Bilayers ◽

Membrane Vesicles ◽

Receptor Site ◽

Single Channels ◽

Planar Lipid Bilayers ◽

Na Channels ◽

Plasma Membrane Vesicles ◽

Voltage Range ◽

Conduction Pathway ◽

Almost All

Single Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers formed from neutral phospholipids and were observed in the presence of batrachotoxin. The batrachotoxin-modified channel activates in the voltage range -120 to -80 mV and remains open almost all the time at voltages positive to -60 mV. Low levels of tetrodotoxin (TTX) induce slow fluctuations of channel current, which represent the binding and dissociation of single TTX molecules to single channels. The rates of association and dissociation of TTX are both voltage dependent, and the association rate is competitively inhibited by Na+. This inhibition is observed only when Na+ is increased on the TTX binding side of the channel. The results suggest that the TTX receptor site is located at the channel's outer mouth, and that the Na+ competition site is not located deeply within the channel's conduction pathway.

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Cloning and Sequence Analysis of the Common α-Subunit Complementary Deoxyribonucleic Acid of Turkey Pituitary Glycoprotein Hormones ,

Poultry Science ◽

10.3382/ps.0702516 ◽

1991 ◽

Vol 70 (12) ◽

pp. 2516-2523 ◽

Cited By ~ 8

Author(s):

DOUGLAS N. FOSTER ◽

LINDA K. FOSTER

Keyword(s):

Sequence Analysis ◽

Deoxyribonucleic Acid ◽

Glycoprotein Hormones ◽

Α Subunit ◽

Complementary Deoxyribonucleic Acid ◽

The Common

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Acute Oxygen Sensing in Heme Oxygenase-2 Null Mice

The Journal of General Physiology ◽

10.1085/jgp.200609591 ◽

2006 ◽

Vol 128 (4) ◽

pp. 405-411 ◽

Cited By ~ 79

Author(s):

Patricia Ortega-Sáenz ◽

Alberto Pascual ◽

Raquel Gómez-Díaz ◽

José López-Barneo

Keyword(s):

Gene Expression ◽

K Channel ◽

Α Subunit ◽

Organ Growth ◽

K Channels ◽

Channel Gene ◽

Sensitive Organ ◽

Stress Dependent ◽

Acute Oxygen Sensing ◽

O2 Sensing

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K+ channels and has been proposed to be the acute O2 sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O2 sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K+ channel α-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K+ channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O2-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K+ channel gene expression but it does not alter the intrinsic O2 sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O2 sensor.

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Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: Cleavage of the common α subunit during apoptosis

Oncogene ◽

10.1038/sj.onc.1204099 ◽

2001 ◽

Vol 20 (3) ◽

pp. 358-366 ◽

Cited By ~ 12

Author(s):

Ki-Woo Kim ◽

Hyun-Ho Chung ◽

Chul-Woong Chung ◽

In-Ki Kim ◽

Masayuki Miura ◽

...

Keyword(s):

Caspase 3 ◽

Α Subunit ◽

Geranylgeranyltransferase I ◽

The Common

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Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase α subunit

The Journal of General Physiology ◽

10.1085/jgp.200910301 ◽

2010 ◽

Vol 135 (2) ◽

pp. 115-134 ◽

Cited By ~ 35

Author(s):

Susan Meier ◽

Neslihan N. Tavraz ◽

Katharina L. Dürr ◽

Thomas Friedrich

Keyword(s):

Binding Site ◽

Critical Role ◽

Aromatic Amino Acids ◽

Cation Binding ◽

Carboxy Terminus ◽

Leakage Currents ◽

Α Subunit ◽

Inward Currents ◽

The Common ◽

Carboxy Terminal

The Na+/K+-ATPase mediates electrogenic transport by exporting three Na+ ions in exchange for two K+ ions across the cell membrane per adenosine triphosphate molecule. The location of two Rb+ ions in the crystal structures of the Na+/K+-ATPase has defined two “common” cation binding sites, I and II, which accommodate Na+ or K+ ions during transport. The configuration of site III is still unknown, but the crystal structure has suggested a critical role of the carboxy-terminal KETYY motif for the formation of this “unique” Na+ binding site. Our two-electrode voltage clamp experiments on Xenopus oocytes show that deletion of two tyrosines at the carboxy terminus of the human Na+/K+-ATPase α2 subunit decreases the affinity for extracellular and intracellular Na+, in agreement with previous biochemical studies. Apparently, the ΔYY deletion changes Na+ affinity at site III but leaves the common sites unaffected, whereas the more extensive ΔKETYY deletion affects the unique site and the common sites as well. In the absence of extracellular K+, the ΔYY construct mediated ouabain-sensitive, hyperpolarization-activated inward currents, which were Na+ dependent and increased with acidification. Furthermore, the voltage dependence of rate constants from transient currents under Na+/Na+ exchange conditions was reversed, and the amounts of charge transported upon voltage pulses from a certain holding potential to hyperpolarizing potentials and back were unequal. These findings are incompatible with a reversible and exclusively extracellular Na+ release/binding mechanism. In analogy to the mechanism proposed for the H+ leak currents of the wild-type Na+/K+-ATPase, we suggest that the ΔYY deletion lowers the energy barrier for the intracellular Na+ occlusion reaction, thus destabilizing the Na+-occluded state and enabling inward leak currents. The leakage currents are prevented by aromatic amino acids at the carboxy terminus. Thus, the carboxy terminus of the Na+/K+-ATPase α subunit represents a structural and functional relay between Na+ binding site III and the intracellular cation occlusion gate.

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KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1710335114 ◽

2017 ◽

Vol 114 (35) ◽

pp. E7367-E7376 ◽

Cited By ~ 17

Author(s):

Rene Barro-Soria ◽

Rosamary Ramentol ◽

Sara I. Liin ◽

Marta E. Perez ◽

Robert S. Kass ◽

...

Keyword(s):

Action Potentials ◽

Potassium Current ◽

Voltage Sensor ◽

Α Subunit ◽

Voltage Range ◽

Gate Opening ◽

Cardiac Action ◽

Repolarization Phase ◽

Voltage Dependent ◽

Salt Secretion

KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coassembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphosphate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.

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The gene for the common α subunit of porcine pituitary glycoprotein hormone

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0070027 ◽

1991 ◽

Vol 7 (1) ◽

pp. 27-34 ◽

Cited By ~ 21

Author(s):

Y. Kato ◽

T. Ezashi ◽

T. Hirai ◽

T. Kato

Keyword(s):

Genomic Library ◽

Consensus Sequence ◽

Transcriptional Unit ◽

Base Substitution ◽

Subunit Gene ◽

Glycoprotein Hormone ◽

Α Subunit ◽

The Common ◽

Flanking Region ◽

Responsive Element

ABSTRACT The gene for the common α subunit of the porcine anterior pituitary glycoprotein hormones was cloned from a genomic library constructed in EMBL3. The nucleotide sequence of the entire coding sequence of the porcine common α-subunit gene was determined in addition to one intron and 1059 and 160 bp of the 5′-and 3′-flanking regions respectively. Southern blot analysis of the porcine genomic DNA indicated that the common α-subunit gene is present as a single copy. The transcriptional unit of the porcine common α subunit spanned about 14kb and contained four exons interrupted by three introns of about 11.5, 1.2 and 0.4kb. The short untranslated sequence in the first exon and the location of the exon/intron junctions at amino acid residues +9/+10 and +71/+72 were highly conserved among the rat, human and bovine common α-subunit genes. In the proximal portion of the 5′-flanking region, one TATA box and one CCAAT box were present. A steroid-responsive element was not found up to 1059 bases upstream from the transcription start site. The potential AP-1 and AP-2 factor-responsive elements were present at three and one positions respectively in the 5′-flanking region. This feature suggests that hypothalamic gonadotrophin-releasing hormone stimulates the expression of the common α-subunit gene predominantly by a signal-transduction system, with the protein kinase C cascade and factors AP-1 and AP-2 as mediators. The cyclic AMP-responsive element was also present at two positions, but a single base substitution was found in each sequence compared with the consensus sequence. The porcine common α-subunit gene has a structure distinct from its counterparts, the porcine FSH-β and LH-β genes, reflecting differential control of their synthesis during gametogenesis.

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Heterologous Facilitation of G Protein-Activated K+ Channels by β-Adrenergic Stimulation via Camp-Dependent Protein Kinase

The Journal of General Physiology ◽

10.1085/jgp.115.5.547 ◽

2000 ◽

Vol 115 (5) ◽

pp. 547-558 ◽

Cited By ~ 44

Author(s):

Carmen Müllner ◽

Dimitry Vorobiov ◽

Amal Kanti Bera ◽

Yasuhito Uezono ◽

Daniel Yakubovich ◽

...

Keyword(s):

G Protein ◽

Slow Component ◽

Xenopus Laevis Oocytes ◽

Adrenergic Stimulation ◽

Current Increase ◽

Girk Channels ◽

Α Subunit ◽

K Channels ◽

Adult Rat ◽

Whole Cell Patch Clamp

To investigate possible effects of adrenergic stimulation on G protein–activated inwardly rectifying K+ channels (GIRK), acetylcholine (ACh)-evoked K+ current, IKACh, was recorded from adult rat atrial cardiomyocytes using the whole cell patch clamp method and a fast perfusion system. The rise time of IKACh was 0.4 ± 0.1 s. When isoproterenol (Iso) was applied simultaneously with ACh, an additional slow component (11.4 ± 3.0 s) appeared, and the amplitude of the elicited IKACh was increased by 22.9 ± 5.4%. Both the slow component of activation and the current increase caused by Iso were abolished by preincubation in 50 μM H89 {N-[2-((p -bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, a potent inhibitor of PKA}. This heterologous facilitation of GIRK current by β-adrenergic stimulation was further studied in Xenopus laevis oocytes coexpressing β2-adrenergic receptors, m2 -receptors, and GIRK1/GIRK4 subunits. Both Iso and ACh elicited GIRK currents in these oocytes. Furthermore, Iso facilitated ACh currents in a way, similar to atrial cells. Cytosolic injection of 30–60 pmol cAMP, but not of Rp-cAMPS (a cAMP analogue that is inhibitory to PKA) mimicked the β2-adrenergic effect. The possibility that the potentiation of GIRK currents was a result of the phosphorylation of the β-adrenergic receptor (β2AR) by PKA was excluded by using a mutant β2AR in which the residues for PKA-mediated modulation were mutated. Overexpression of the α subunit of G proteins (Gαs) led to an increase in basal as well as agonist-induced GIRK1/GIRK4 currents (inhibited by H89). At higher levels of expressed Gαs, GIRK currents were inhibited, presumably due to sequestration of the β/γ subunit dimer of G protein. GIRK1/GIRK5, GIRK1/GIRK2, and homomeric GIRK2 channels were also regulated by cAMP injections. Mutant GIRK1/GIRK4 channels in which the 40 COOH-terminal amino acids (which contain a strong PKA phosphorylation consensus site) were deleted were also modulated by cAMP injections. Hence, the structural determinant responsible is not located within this region. We conclude that, both in atrial myocytes and in Xenopus oocytes, β-adrenergic stimulation potentiates the ACh-evoked GIRK channels via a pathway that involves PKA-catalyzed phosphorylation downstream from β2AR.

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