Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

2021 ◽  
Author(s):  
Enes Akyuz ◽  
Betul Koklu ◽  
Arda Uner ◽  
Efthalia Angelopoulou ◽  
Yam Nath Paudel
Keyword(s):  
Kir Channel ◽  
Inwardly Rectifying

Role of inwardly rectifying K+ channels in K+-induced cerebral vasodilatation in vivo

2000 ◽  
Vol 279 (6) ◽  
pp. H2704-H2712 ◽  
Author(s):  
Sophocles Chrissobolis ◽  
James Ziogas ◽  
Yi Chu ◽  
Frank M. Faraci ◽  
Christopher G. Sobey
Keyword(s):  
Basilar Artery ◽  
Channel Activity ◽  
Atpase Inhibitor ◽  
Kir Channel ◽  
Cerebral Vasodilatation ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Inwardly Rectifying

We tested whether activation of inwardly rectifying K+ (Kir) channels, Na+-K+-ATPase, or nitric oxide synthase (NOS) play a role in K+-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K+] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 ± 1, 27 ± 4, 35 ± 4, 43 ± 12, and 47 ± 16%, respectively). Responses to K+ were inhibited by ∼50% by the Kir channel inhibitor BaCl2 (30 and 100 μM). In contrast, neither ouabain (1–100 μM, a Na+-K+-ATPase inhibitor) nor N G-nitro-l-arginine (30 μM, a NOS inhibitor) had any effect on K+-induced vasodilatation. These concentrations of K+ also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 μM BaCl2. RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K+-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na+-K+-ATPase, or NOS.

scholarly journals Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa

2021 ◽  
Vol 22 (11) ◽  
pp. 5972
Author(s):  
Giulia Poli ◽  
Sonia Hasan ◽  
Silvia Belia ◽  
Marta Cenciarini ◽  
Stephen J. Tucker ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Knock Out ◽  
Gene Ablation ◽  
Kir Channel ◽  
K Concentration ◽  
Knock Out Mice ◽  
Inwardly Rectifying ◽  
Dependent Processes ◽  
K Permeability

The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K+ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H+ (pHi) and extracellular K+ concentration [K+]o, and hence provides a link between pHi and [K+]o changes and membrane potential. The intrinsic pHi sensitivity of Kir5.1 suggests a possible role for this channel in the pHi-dependent processes that take place during fertilization. However, despite the localization of Kir5.1 in murine spermatozoa, and its increased expression with age and sexual maturity, the role of the channel in sperm morphology, maturity, motility, and fertility is unknown. Here, we confirmed the presence of Kir5.1 in spermatozoa and showed strong expression of Kir4.1 channels in smooth muscle and epithelial cells lining the epididymal ducts. In contrast, Kir4.2 expression was not detected in testes. To examine the possible role of Kir5.1 in sperm physiology, we bred mice with a deletion of the Kcnj16 (Kir5.1) gene and observed that 20% of Kir5.1 knock-out male mice were infertile. Furthermore, 50% of knock-out mice older than 3 months were unable to breed. By contrast, 100% of wild-type (WT) mice were fertile. The genetic inactivation of Kcnj16 also resulted in smaller testes and a greater percentage of sperm with folded flagellum compared to WT littermates. Nevertheless, the abnormal sperm from mutant animals displayed increased progressive motility. Thus, ablation of the Kcnj16 gene identifies Kir5.1 channel as an important element contributing to testis development, sperm flagellar morphology, motility, and fertility. These findings are potentially relevant to the understanding of the complex pHi- and [K+]o-dependent interplay between different sperm ion channels, and provide insight into their role in fertilization and infertility.

scholarly journals Gating Sensitive Residues In The Pore Of An Inwardly Rectifying Potassium (Kir) Channel

2009 ◽  
Vol 96 (3) ◽  
pp. 462a
Author(s):  
Murali K. Bollepalli ◽  
Markus Rapedius ◽  
Philip Fowler ◽  
Man-Jiang Xie ◽  
Lijun Shang ◽  
...  
Keyword(s):  
Kir Channel ◽  
Inwardly Rectifying

Altered Regulation of Potassium and Calcium Channels by GABAB and Adenosine Receptors in Hippocampal Neurons From Mice Lacking Gαo

2000 ◽  
Vol 83 (2) ◽  
pp. 1010-1018 ◽  
Author(s):  
Gabriela J. Greif ◽  
Deborah L. Sodickson ◽  
Bruce P. Bean ◽  
Eva J. Neer ◽  
Ulrike Mende
Keyword(s):  
Time Constant ◽  
Hippocampal Neurons ◽  
Ionic Currents ◽  
Absolute Requirement ◽  
Voltage Dependent ◽  
Hippocampal Ca3 ◽  
Ca3 Neurons ◽  
Inwardly Rectifying ◽  
G Protein Coupled

To examine the role of Go in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gαo. In CA3 neurons from Gαo −/− mice, 2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in Gαo +/+ littermates. However, the kinetics of transmitter action were dramatically altered in Gαo −/− mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gαo −/− mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gαo +/+ mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+ currents and K+currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gαo, some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gαo. However, modulation is changed in the absence of Gαo in having much slower recovery kinetics. A likely possibility is that the very abundant Gαo is normally used but, when absent, can readily be replaced by G proteins with different properties.

Modulation of cell membrane potential in cultured vascular endothelium

1996 ◽  
Vol 270 (3) ◽  
pp. C819-C824 ◽  
Author(s):  
L. Vaca ◽  
A. Licea ◽  
L. D. Possani
Keyword(s):  
Membrane Potential ◽  
Cell Membrane ◽  
Cell Membrane Potential ◽  
Resting Potential ◽  
Similar Response ◽  
Aortic Endothelial Cells ◽  
Ionic Conductances ◽  
Selective Channel ◽  
Inwardly Rectifying

The present study explores the role of different ionic conductances in the regulation of membrane potential under resting conditions and after bradykinin (BK) or thapsigargin (TG) stimulation of cultured bovine aortic endothelial cells. Under resting conditions, the cell membrane potential observed was -62+/- 5 mV. The main conductance under these conditions is an inwardly rectifying potassium (IRK) channel. Application of 50 nM BK induced a transient hyperpolarization to -87 +/- 4 mV followed by sustained depolarization to -35 +/- 5 mV. The transient hyperpolarization was eliminated by 1 microM noxiustoxin, a blocker of calcium-activated postassium channels (K(Ca)). the sustained depolarization induced by BK was prevented by incubating the cells with the calcium channel blocker lanthanum. TG evoked a similar response in membrane potential, with the exception that the onset of the hyperpolarization was slower compared with BK. The results presented here indicate that the cell resting potential is maintained at -62 +/- 2 mV by the IRK channel. BK or TG stimulation induces a transient hyperpolarization of approximately -20 mV produced by activation of a KCa. This hyperpolarization is followed by a sustained depolarization produced by activation of a calcium-selective channel sensitive to lanthanum.

Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes

2020 ◽  
Vol 52 (12) ◽  
pp. 856-860
Author(s):  
Annalisa Blasetti ◽  
Valeria Castorani ◽  
Laura Comegna ◽  
Simone Franchini ◽  
Giovanni Prezioso ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Therapeutic Potential ◽  
Insulin Requirement ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Binding Function ◽  
Inwardly Rectifying

AbstractDiabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA’s loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

scholarly journals Unconventional Role of the Inwardly Rectifying Potassium Channel Kir2.2 as a Constitutive Activator of RelA in Cancer

2012 ◽  
Vol 73 (3) ◽  
pp. 1056-1062 ◽  
Author(s):  
Inkyoung Lee ◽  
Sook-Ja Lee ◽  
Tong Mook Kang ◽  
Won Ki Kang ◽  
Chaehwa Park
Keyword(s):  
Potassium Channel ◽  
Inwardly Rectifying Potassium Channel ◽  
Inwardly Rectifying

scholarly journals Fyn-tau Ablation Modifies PTZ-Induced Seizures and Post-seizure Hallmarks of Early Epileptogenesis

2020 ◽  
Vol 14 ◽  
Author(s):  
Marson Putra ◽  
Sreekanth Puttachary ◽  
Guanghao Liu ◽  
Gloria Lee ◽  
Thimmasettappa Thippeswamy
Keyword(s):  
Double Knockout ◽  
Neuroprotective Effects ◽  
Western Blots ◽  
Seizure Reduction ◽  
Genetic Ablation ◽  
Genetic Deletion ◽  
Convulsive Seizures ◽  
Epilepsy Models ◽  
Inwardly Rectifying

Both Fyn and tau have been associated with neuronal hyperexcitability and neurotoxicity in many tauopathies, including Alzheimer's disease (AD). Individual genetic ablation of fyn or tau appears to be protective against aberrant excitatory neuronal activities in AD and epilepsy models. It is, however, still unknown whether ablation of both Fyn and tau can likely elicit more profound anti-seizure and neuroprotective effects. Here, we show the effects of genetic deletion of Fyn and/or tau on seizure severity in response to pentylenetetrazole (PTZ)-induced seizure in mouse models and neurobiological changes 24 h post-seizures. We used Fyn KO (fyn−/−), tau KO (tau−/−), double knockout (DKO) (fyn−/−/tau−/−), and wild-type (WT) mice of the same genetic background. Both tau KO and DKO showed a significant increase in latency to convulsive seizures and significantly decreased the severity of seizures post-PTZ. Although Fyn KO did not differ significantly from WT, in response to PTZ, Fyn KO still had 36 ± 8% seizure reduction and a 30% increase in seizure latency compared to WT. Surprisingly, in contrast to WT, Fyn KO mice showed higher mortality in <20 min of seizure induction; these mice had severe hydrocephalous. None of the tau−/− and DKO died during the study. In response to PTZ, all KO groups showed a significant reduction in neurodegeneration and gliosis, in contrast to WT, which showed increased neurodegeneration [especially, parvalbumin (PV)-GABAergic interneurons] and gliosis. DKO mice had the most reduced gliosis. Immunohistochemically, phospho-tau (AT8, pS199/S202), Fyn expression, as well as Fyn-tau interaction as measured by PLA increased in WT post-PTZ. Moreover, hippocampal Western blots revealed increased levels of AT8, tyrosine phospho-tau (pY18), and phosphorylated Src tyrosine family kinases (pSFK) in PTZ-treated WT, but not in KO, compared to respective controls. Furthermore, PV interneurons were protected from PTZ-induced seizure effects in all KO mice. The levels of inwardly rectifying potassium (Kir 4.1) channels were also downregulated in astrocytes in the WT post-PTZ, while its levels did not change in KO groups. Overall, our results demonstrated the role of Fyn and tau in seizures and their impact on the mediators of early epileptogenesis in PTZ model.

The role of an inwardly rectifying chloride conductance in postsynaptic inhibition

1994 ◽  
Vol 72 (1) ◽  
pp. 273-284 ◽  
Author(s):  
K. Staley
Keyword(s):  
Protein Kinase ◽  
Dentate Gyrus ◽  
Maximum Amplitude ◽  
Chloride Conductance ◽  
Equilibrium Potential ◽  
Inward Rectification ◽  
Tetraacetic Acid ◽  
Recording Time ◽  
Inwardly Rectifying

1. The relationship of the activation of a voltage-sensitive chloride conductance [GCl(V)] to the chloride transmembrane equilibrium potential (ECl) and the consequent role of this conductance in determining the effect of the gamma-aminobutyric acid-A (GABAA) receptor-mediated transmembrane chloride (Cl-) flux were investigated with the use of whole-cell recordings in the CA1 and dentate gyrus regions of adult rat hippocampal slice preparations. 2. GCl(V) was inwardly rectifying, with significant conductance only at membrane potentials more negative than ECl. For all tested neuronal Cl- concentrations, the activation of GCl(V) could be described by a Boltzman equation with an average half-activation voltage 15 mV negative to ECl, a slope factor of 14 mV, and a maximum conductance of 5 microS. There was no time-dependent inactivation of GCl(V). 3. GCl(V) was modulated by intracellular divalent cations. When magnesium was omitted from the electrode solution, the inward rectification of GCl(V) was unchanged, but the maximum amplitude of GCl(V) increased by a factor of 1.7. GCl(V) was blocked by bath application of 100 microM zinc (Zn2+), but not when 1–6 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) were present in the electrode solution. 4. GCl(V) was increased by 10 microM norepinephrine, and by activation of protein kinase A (PKA) with 1 mM 8-bromoadenosine cyclic monophosphate (8-Br cAMP). GCl(V) was blocked by activation of protein kinase C (PKC) with 10 microM phorbol 12,13-dibutyrate (PdBu) or 1-oleoyl-2-acetyl-sn-glycerol (OAG). 5. GCl(V) was present in all tested CA1 pyramidal neurons but no dentate gyrus neurons. In standard extracellular solution, the amplitude of GCl(V) was initially negligible but increased with recording time, suggesting that under normal conditions GCl(V) is blocked by an endogenous divalent cation or downregulated by PKC. 6. In current-clamp recordings, the steady-state resting membrane potential (RMP) diminished with Cl- loading, from -73 mV (4 mM electrode Cl-) to -27 mV (131 mM electrode Cl-). When GCl(V) was blocked with PdBu, there was no change in the RMP with Cl- loading. When electroneutral Cl- transport was blocked, voltage-clamp experiments using electrode Cl- concentrations of 4–131 mM demonstrated that ECl changed in parallel with the holding potential, but not when GCl(V) was blocked by PdBu.(ABSTRACT TRUNCATED AT 400 WORDS)

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