Potassium channel activators. Medical search. Frequent questions

Background: THIK-1, THIK-2 and TREK-1 and all belong to family of two-pore-domain potassium channel (K2P channels). (uni-marburg.de)
In addition, TREK channels belonging to the family of two-pore domain (K2P) potassium channels, and especially TREK-1, are abundantly expressed in NG neurons. (uvigo.es)

When cultures are treated with the K + -channel activators cromakalim and diazoxide both the [Ca 2+ ] i fluctuations and the neuronal death are abolished. (northwestern.edu)
Purpose: To evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension. (bvsalud.org)
Conclusions: ATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma. (bvsalud.org)

We have identified cromakalim prodrug 1 (CKLP1), a novel water-soluble ATP-sensitive potassium channel opener, as a new ocular hypotensive agent. (bvsalud.org)

is a potent ATP-sensitive potassium (KATP) channel activator. (stockhouse.com)
ATP-sensitive K+ (KATP) channels have been proposed to be the target for hyperpolarizing vasodilators. (semanticscholar.org)

Rottlerin is a potent large conductance potassium channel (BKCa++) opener. (wikipedia.org)
Our results suggest that arginine 92 of THIK-1 and the C2-P1 linker region of K2P channels play an important role in the binding of IBMX, and perhaps other more potent drugs, to the channel. (uni-marburg.de)
3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. (immune-system-research.com)

This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. (nih.gov)
This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). (nih.gov)
Knockdown of inwardly rectifying potassium channel Kir2.2 suppresses tumorigenesis by inducing reactive oxygen species-mediated cellular senescence. (nih.gov)

Abele, AE & Miller, RJ 1990, ' Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons ', Neuroscience Letters , vol. 115, no. 2-3, pp. 195-200. (northwestern.edu)
Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech. (harvard.edu)
In hypothalamic neurons, modulators such as neuropeptide Y (NPY) and adenosine depress glutamatergic transmission by either a pertussis toxin (PTx)-sensitive G-protein-coupled pathway or by inhibition of voltage-activated calcium channels (VACCs). (jneurosci.org)
This increased intrinsic excitability of DCN neurons is accompanied by a reduction in after-hyperpolarization currents mediated by small-conductance calcium-activated potassium (SK) channels. (foundationdystoniaresearch.org)

The inward-rectifier potassium channel family (also known as 2-TM channels) include the strong inward-rectifier channels (K ir 2.x), the G-protein-activated inward-rectifier channels (K ir 3.x) and the ATP-sensitive channels (K ir 6.x), which combine with sulphonylurea receptors. (tocris.com)

Hougaard et al (2009) Selective activation of the SK1 subtype of human small-conductance Ca2+-activated K+ channels by 4-(2-methyoxy-phenylcarbamoyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (GW542573X) is dependent on serine 298 in Mol.Pharmacol. (tocris.com)

Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction. (harvard.edu)
Cerebellar ataxia by enhanced Ca(V)2.1 currents is alleviated by Ca2+-dependent K+-channel activators in Cacna1a(S218L) mutant mice. (harvard.edu)
ML277 provides insights and a tool to investigate the gating mechanism of KCNQ1 channels, and our study reveals a new strategy for treating long QT syndrome by specifically enhancing the AO state of native I Ks currents. (elifesciences.org)
After the application of both riluzole and ML67-33 activators, the three neuronal types responded with outward currents similar to those transported by TREK channels. (uvigo.es)
Furthermore, both increased temperature and intracellular acidification produced larger potassium currents comparable to those driven through TREK, as well as conductance increases in three NG neuronal types. (uvigo.es)

The large-conductance Ca 2+ -activated K + channel (Maxi K + channel) inhibitor iberiotoxin significantly prevented the relaxations induced by lower concentrations (3 and 10 µmol/l) of nicorandil. (karger.com)
Discovery of Novel Activators of Large-Conductance Calcium-Activated Potassium Channels for the Treatment of Cerebellar Ataxia. (harvard.edu)

Mallotoxin is also a hERG potassium channel activator. (wikipedia.org)
K V 11.1 (hERG) and K ir 6 (K ATP ) channel blocker. (tocris.com)
In particular, TBAJ-587 inhibits hERG channel minimally and attenuates inhibition of the cardiac potassium channel protein coded by the hERG, which is important for cardiac repolarization. (immune-system-research.com)

Neuropathic pain and Kv7 voltage-gated potassium channels: The potential role of Kv7 activators in the treatment of neuropathic pain. (iasp-pain.org)

The ATP-sensitive K + (K ATP ) channel blocker glibenclamide only partially attenuated the relaxant responses to nicorandil (at 100 and 300 µmol/l). (karger.com)
These results suggest that nicorandil relaxes bovine tracheal smooth muscle through 2 mechanisms: opening of K ATP channels and activation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. (karger.com)
Nicorandil may also activate Maxi K + channels, possibly through the NO-cGMP pathway, and the interaction of K ATP channels and Maxi K + channels may affect the relaxant effect of nicorandil in bovine tracheal smooth muscle. (karger.com)
Taira N: Nicorandil as a hybrid between nitrates and potassium channel activators. (karger.com)

The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (bvsalud.org)

The application of H89 (PKA inhibitor) and forskolin (PKA activator) did not modify the effects of IBMX on the channel. (uni-marburg.de)

Other BKCa++ channel openers are reported to limit the mitochondrial calcium overload due to ischemia. (wikipedia.org)
BKCa++ channels reside in the inner mitochondrial membrane and their activation is proposed to increase K+ accumulation in mitochondria. (wikipedia.org)
This may result in less mitochondrial damage and therefore greater contractility since there is a decrease in apoptosis compared to no stimulation of BKCa++ channels. (wikipedia.org)
In addition, Nar stimulates the mitochondrial calcium-dependent potassium channel (mitoBKCa), which causes an influx of potassium ions, a mild depolarization, and a decrease in the mitochondrial matrix calcium uptake, all of which contribute to stabilizing the mitochondria during cellular damage [ 3 , 4 ]. (hindawi.com)
Unicycive Therapeutics Inc. has announced key efficacy findings with UNI-494 in animal models of geographic atrophy (GA). UNI-494 is a mitochondrial potassium channel (mitoKATP) activator in development for treating diseases affected by mitochondrial dysfunction, such as kidney, liver and ocular diseases. (bioworld.com)

Smooth muscle cells express Kv7.4 and Kv7.5 voltage-dependent potassium channels, which have each been implicated as regulators of smooth muscle contractility, though they display different sensitivities to signaling via cAMP/protein kinase A (PKA) and protein kinase C (PKC). (aspetjournals.org)
The inhibition could be mimicked by the L-type calcium channel blocker nimodipine (1 μ m ) as well as by protein kinase C (PKC) activators phorbol 12,13-dibutyrate (10 μ m ) and phorbol 12-myristate 13-acetate (500 n m ), and blocked by the PKC inactivator (±)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine (200 μ m ), suggesting a mechanism involving PKC modulation of L-type calcium channels. (jneurosci.org)

Kv7 family channels mediate a voltage-dependent outward flux of potassium ions, which contributes to the establishment of negative membrane potentials in many cell types. (aspetjournals.org)

Upon membrane depolarization, the KCNQ1 potassium channel opens at the intermediate (IO) and activated (AO) states of the stepwise voltage-sensing domain (VSD) activation. (elifesciences.org)

Repurposing Kir6/Sur2 Channel Activator Minoxidil To Arrests Growth Of Gynecologic Cancers. (luc.edu)

Potassium channels whose activation is dependent on intracellular calcium concentrations. (harvard.edu)

Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium. (semanticscholar.org)

Forskolin, an activator of the cAMP/PKA pathway, increased wild-type Kv7.5 but not wild-type Kv7.4 current amplitude. (aspetjournals.org)
Forskolin treatment reduced the sensitivity of Kv7.5 channels to Ciona intestinalis voltage-sensing phosphatase (Ci-VSP)-induced PIP 2 depletion, whereas activation of PKC with phorbol-12-myristate-13-acetate potentiated the Ci-VSP-induced decline in Kv7.5 current amplitude. (aspetjournals.org)

Conclusions: IMBX can block TREK-1 channels though the PKA pathway, it also can bind to the extracellular side of THIK-1 or THIK-2, leading to a direct block of the channels. (uni-marburg.de)

In this study, we demonstrate that use of the Kv11.1 K(+) channel activator NS1643 inhibits tumor growth in an in vivo model of breast cancer. (luc.edu)

KCNE1 suppresses the IO state so that the I Ks channel opens only to the AO state. (elifesciences.org)

We propose that use of Kv11.1 channels activators could be considered as a possible pharmacological strategy against breast tumors. (luc.edu)
Introduction Calcium channel blockers (CCB) and betablockers (BB) intoxications represent 40% of the pharmacological poisoning cases in the USA and account for 65% of deaths determined by cardiovascular drugs1. (doczz.net)

To analyze the surface expression of the channel we used HA-tagged THIK-2 and thus quantified the copy number of the channels at the cell membrane using an antibody-based assay. (uni-marburg.de)
These data indicate that the ER retention/retrieval signal RRR can prevent the THIK-2 export to the cell membrane, leading to the silence of the channel. (uni-marburg.de)

We expressed chimeric channels composed of different components of the Kv7.4 and Kv7.5 α -subunits in vascular smooth muscle cells to determine which components are essential for enhancement or inhibition of channel activity. (aspetjournals.org)

cDNAs encoding functional maxi KCa channel alpha-subunits (hslo) were cloned from human myometrium. (semanticscholar.org)
The present studies identify distinct functional domains that confer differential sensitivities of Kv7.4 and Kv7.5 to stimulatory and inhibitory signaling and reveal structural features of the channel subunits that determine their biophysical properties. (aspetjournals.org)
functional channels form as homo- or hetero-tetramers of α -subunits ( Delmas and Brown, 2005 ). (aspetjournals.org)
In the heart, KCNQ1 associates with KCNE1 subunits to form I Ks channels that regulate heart rhythm. (elifesciences.org)

Other BKCa++ channel openers (NS1619, NS11021 and DiCl-DHAA) have been reported to have cardio-protective effects after ischemic-reperfusion injury. (wikipedia.org)

9: 241-246 Calcium channel blockers, beta-blockers and digitalis poisoning: management in the emergency room V. OJETTI, A. MIGNECO, F. BONONI, A. DE LORENZO*, N. GENTILONI SILVERI Department of Emergency Medicine, Catholic University - Rome (Italy) *Human Nutrition Unit, University of Tor Vergata - Rome (Italy) Abstract. (doczz.net)

Ca(2+)-activated K(+) channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model. (harvard.edu)
Calcium Channel Blocker and Beta Blocker Intoxication Although CCB and BB have different mechanisms of action, their cardiovascular ef- fect are similar. (doczz.net)

Significant changes shared by the fly species belong to the expression of genes involved in processes such as oxidation-reduction process, iron-ion binding, and voltage-gated potassium-channel activity. (nature.com)

Opening these channels is beneficial for post-ischemic changes in vasodilation. (wikipedia.org)
ATP-sensitive K+ channels mediate vasodilation produced by lemakalim in rabbit pulmonary artery. (semanticscholar.org)

The preventive effect of iberiotoxin was markedly enhanced under the blockade of K ATP channels with glibenclamide. (karger.com)

Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP‐sensitive potassium channels. (semanticscholar.org)

Removal of this additional domain (mutant THIK-2Δ6-24) or mutation of the RRR motif to AAA (THIK-2AAA mutant) gave rise to a measurable potassium current. (uni-marburg.de)

The IC50 of the direct effect of IBMX on THIK-1 channels was about 120 μM. (uni-marburg.de)
GABA A Potentiates the effect of GABA, prolonging Cl - channel opening and hyperpolarising the cell. (litfl.com)
In the present work, the effect of sensory stimuli such as temperature and pH was studied in the TREK channels of different NG neuronal types. (uvigo.es)

An activator of SK channels reduces DCN neuron firing frequency in acute cerebellar slices and improves the dystonic gait of Atcayji-hes mice. (foundationdystoniaresearch.org)

The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. (semanticscholar.org)

The activation of BKCa++ channels by rottlerin relaxes coronary smooth muscle and improves myocardial perfusion after cardioplegia. (wikipedia.org)

Calcium channel blockers and beta-blockers intoxications account for up to 65% of deaths for cardiovascular drugs, causing severe clinical symptoms refractory to standard medications. (doczz.net)

ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells. (semanticscholar.org)

Basal activation of ATP-sensitive potassium channels in murine colonic smooth muscle cell. (semanticscholar.org)
ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. (semanticscholar.org)
SIGNIFICANCE STATEMENT Kv7.4 and Kv7.5 channels are known signal transduction intermediates and drug targets for regulation of smooth muscle tone. (aspetjournals.org)
These findings may improve our understanding of the roles of these channels in smooth muscle physiology and disease, particularly in conditions where Kv7.4 and Kv7.5 are differentially expressed. (aspetjournals.org)

To identify the binding site of IBMX on THIK-1 we mutated all amino acids of the helical cap one by one and screened for changes in IBMX sensitivity of the channels. (uni-marburg.de)
The prominence of Kv7 channels as regulators of electrical excitability may be ascribed to their unique properties, such as a very negative threshold of activation (negative to −50 mV), absence of time-dependent inactivation, and high sensitivity to signal transduction pathways that influence their probability of opening, either positively or negatively ( Delmas and Brown, 2005 ). (aspetjournals.org)

Here, we tested modulations of human KCNQ1 channels by an activator ML277 in Xenopus oocytes. (elifesciences.org)

Potassium ion (K(+)) channels have been recently found to play a critical role in cancer biology. (luc.edu)

Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes-An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca). Cells. (harvard.edu)
Methods: Whole cell recording patch clamp measurements in mammalian cells was used to analyze K2P channels mentioned above. (uni-marburg.de)

Anatomy22

Organisms15

Diseases8

Chemicals and Drugs155

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes37

Disciplines and Occupations3

Technology, Industry, Agriculture1

Information Science3

Family of two-pore-domain2

Diazoxide3

Cromakalim1

KATP2

Potent3

Inwardly3

Neurons4

Inward-rectifier1

Small-conductance1

Currents5

Large conductance2

HERG3

Voltage-gated po1

Nicorandil4

Cardiac1

Inhibitor1

Mitochondrial5

Protein2

Ions1

Depolarization1

Kir61

Intracellular1

Characterization1

Forskolin2

Extracellular1

Inhibits1

Suppresses1

Pharmacological2

Membrane2

Inhibition1

Subunits4

Openers1

Abstract1

Blocker2

Species1

Vasodilation2

Glibenclamide1

Nitric1

Mutant1

Effect3

Mice1

Airway1

Myocardial1

Beta-blockers1

Regulate1

Smooth muscle4

Sensitivity2

Human1

Role1

Cells2