Anomalous Scaling of Parasitic Capacitance in FETs with a High-K Channel Material

The patch-clamp technique for recording single-channel currents across cell membranes was applied to single turtle colon epithelial cells isolated with hyaluronidase. With electrodes fabricated from Corning #7052 glass, high-resistance seals were consistently formed to these cells. In on-cell patches with low K (2.5 mM) in the pipette and high K (114.5 mM) in the bath, outward K currents were recorded that had a slope conductance of 17 pS and a reversal potential greater than -70 mV. Currents through this K channel were blocked by lidocaine, quinidine, and barium. These agents also block a cell swelling-induced K conductance identified by macroscopic current measurements in the basolateral membranes of the intact colonic epithelium, suggesting that the 17 pS K channel identified by single-channel recording in isolated turtle colon cells may be responsible for this macroscopically defined K conductance.

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Selective Proton-Mediated Transport by Electrogenic K+-Binding Macrocycles

Chemistry ◽

10.3390/chemistry2010003 ◽

2020 ◽

Vol 2 (1) ◽

pp. 11-21

Author(s):

Yu-Hao Li ◽

Shao-Ping Zheng ◽

Dawei Wang ◽

Mihail Barboiu

Keyword(s):

Ion Channels ◽

Therapeutic Agents ◽

K Channel ◽

Transport Activity ◽

Selective Activation ◽

K Channels ◽

High K ◽

Carbonyl Cyanide ◽

Self Assembled ◽

K Transport

Synthetic K+-binding macrocycles have potential as therapeutic agents for diseases associated with KcsA K+ channel dysfunction. We recently discovered that artificial self-assembled n-alkyl-benzoureido-15-crown-5-ether form selective ion-channels for K+ cations, which are highly preferred to Na+ cations. Here, we describe an impressive selective activation of the K+ transport via electrogenic macrocycles, stimulated by the addition of the carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP) proton carrier. The transport performances show that both the position of branching or the size of appended alkyl arms favor high transport activity and selectivity SK+/Na+ up to 48.8, one of the best values reported up to now. Our study demonstrates that high K+/Na+ selectivity obtained with natural KcsA K+ channels is achievable using simpler artificial macrocycles displaying constitutional functions.

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Endothelium-Independent Vasodilatory Effects of Isodillapiolglycol Isolated from Ostericum citriodorum

Molecules ◽

10.3390/molecules25040885 ◽

2020 ◽

Vol 25 (4) ◽

pp. 885 ◽

Cited By ~ 1

Author(s):

Tengshuo Luo ◽

Zewei Chen ◽

Fengyun Wang ◽

Shanshan Yin ◽

Pan Liu ◽

...

Keyword(s):

Smooth Muscle ◽

Channel Blocker ◽

Ethyl Acetate Extract ◽

K Channel ◽

Krebs Solution ◽

Native Range ◽

Sprague Dawley ◽

Independent Manner ◽

High K ◽

Voltage Dependent

Ostericum citriodorum is a plant with a native range in China used in herbal medicine for treating angina pectoris. In this study, we investigated the vasodilatory effects of isodillapiolglycol (IDG), which is one of the main ingredients isolated from O. citriodorum ethyl acetate extract, in Sprague–Dawley rat aortic rings, and measured intracellular Ca2+ ([Ca2+]in) using a molecular fluo-3/AM probe. The results show that IDG dose-dependently relaxed endothelium-intact or -denuded aortic rings pre-contracted with noradrenaline (NE) or potassium chloride (KCl), and inhibited CaCl2-induced contraction in high K+ depolarized aortic rings. Tetraethyl ammonium chloride (a Ca2+-activated K+ channel blocker) or verapamil (an L-type Ca2+ channel blocker) significantly reduced the relaxation of IDG in aortic rings pre-contracted with NE. In vascular smooth muscle cells, IDG inhibited the increase in [Ca2+]in stimulated by KCl in Krebs solution; likewise, IDG also attenuated the increase in [Ca2+]in induced by NE or subsequent supplementation of CaCl2. These findings demonstrate that IDG relaxes aortic rings in an endothelium-independent manner by reducing [Ca2+]in, likely through inhibition of the receptor-gated Ca2+ channel and the voltage-dependent Ca2+ channel, and through opening of the Ca2+-activated K+ channel.

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Angiotensin II type 2 receptor regulates ROMK-like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation

AJP Renal Physiology ◽

10.1152/ajprenal.00141.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. F833-F843 ◽

Cited By ~ 13

Author(s):

Yuan Wei ◽

Yi Liao ◽

Beth Zavilowitz ◽

Jin Ren ◽

Wen Liu ◽

...

Keyword(s):

Collecting Duct ◽

No Synthase ◽

K Channel ◽

Ang Ii ◽

Cortical Collecting Duct ◽

Channel Activity ◽

High K ◽

Pka Pathway

The kidney adjusts K+ excretion to match intake in part by regulation of the activity of apical K+ secretory channels, including renal outer medullary K+ (ROMK)-like K+ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K+ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K+ (HK)-fed but not normal K+ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K+-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway.

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Docosahexaenoic Acid-Induced Vasorelaxation in Hypertensive Rats: Mechanisms of Action

Biological Research For Nursing ◽

10.1177/109980040000200202 ◽

2000 ◽

Vol 2 (2) ◽

pp. 85-95 ◽

Cited By ~ 41

Author(s):

Mary B. Engler ◽

Marguerite M. Engler

Keyword(s):

Nitric Oxide ◽

Inhibitory Effect ◽

Significant Inhibition ◽

Isometric Tension ◽

K Channel ◽

Omega 3 ◽

Hypertensive Rats ◽

Blood Pressure Lowering Effect ◽

K Channels ◽

High K

The authors investigated the vasorelaxant properties of the omega-3 fatty acid, docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium-derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1-100 mol/l) relaxation was examined following contraction to norepinephrine (NE) (10– 6 mol/l) or high-K+ (80 mmol/l) solution in the presence and absence of various inhibitors and calcium-containing solution. DHA acid induced a significant vasorelaxant effect in both NE and high-K+-induced contracted SHR aortic rings, although DHA relaxations were greater in high-K+-induced contracted rings. In the absence of extracellular calcium, DHA (5-30 mol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N•-nitro-L-arginine methyl ester hydrochloride (100 mol/l) had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at• 30 mol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl-ammonium, also had an inhibitory effect on DHA-induced relaxation. These results indicate that DHA’s vasorelaxant actions in SHR aorta are independent of endothelium-derived nitric oxide; however, at DHA concentrations• 30 mol/l, vasodilatory prostanoids that activate AT Psensitive K+ channels (KATP) may be involved. At lower concentrations, DHA-induced relaxation appears to be attributed to modulation of intracellular Ca2+release and L-type Ca2+channels in vascular smooth muscle cells. The vasorelaxant properties of DHA may contribute, in part, to the blood pressure–lowering effect of dietary fish oil in this hypertensive model.

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Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL

AJP Renal Physiology ◽

10.1152/ajprenal.2001.280.2.f223 ◽

2001 ◽

Vol 280 (2) ◽

pp. F223-F230 ◽

Cited By ~ 22

Author(s):

Ruimin Gu ◽

Yuan Wei ◽

Houli Jiang ◽

Michael Balazy ◽

Wenhui Wang

Keyword(s):

Gas Chromatography Mass Spectrometry ◽

K Channel ◽

Thick Ascending Limb ◽

Patch Clamp Technique ◽

Open Probability ◽

Deficient Diet ◽

K Channels ◽

Medullary Thick Ascending Limb ◽

High K

We have used the patch-clamp technique to study the effect of dietary K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by the number of channels in a patch and the open probability ( NP o), of the 30- and 70-pS K channels, was 0.18 and 0.11, respectively, in the mTAL from rats on a K-deficient diet. In contrast, NP o of the 30- and 70-pS K channels increased to 0.60 and 0.80, respectively, in the tubules from animals on a high-K diet. The concentration of 20-hydroxyeicosatetraenoic acid (20-HETE) measured with gas chromatography-mass spectrometry was 0.8 pg/μg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/μg protein in the tubules from rats on a K-deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA), agents that inhibit the formation of 20-HETE, had no significant effect on the activity of the 30-pS K channels. However, DDMS/17-ODYA significantly increased the activity of the apical 70-pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P-450 metabolism of arachidonic acid increased NP o from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the sensitivity of the 70-pS K channel to 20-HETE was the same between rats on a high-K diet and on a K-deficient diet. Finally, the pretreatment of the tubules with DDMS increased NP o of the 70-pS K channels in the mTAL from rats on a K-deficient diet to 0.76. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70-pS K channels in the mTAL from rats on a K-deficient diet.

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Endothelium-dependent responses in human isolated thyroid arteries from donors

Journal of Endocrinology ◽

10.1677/joe.0.1810379 ◽

2004 ◽

Vol 181 (3) ◽

pp. 379-384 ◽

Cited By ~ 16

Author(s):

B Torondel ◽

JM Vila ◽

G Segarra ◽

P Lluch ◽

P Medina ◽

...

Keyword(s):

Nitric Oxide ◽

Dominant Role ◽

Human Thyroid ◽

K Channel ◽

Organ Donors ◽

Inhibitory Effects ◽

K Channels ◽

High K ◽

Inwardly Rectifying ◽

Endothelium Dependent Relaxation

The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect was not modified by indomethacin and was only partly reduced by L-NMMA, but was abolished in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA was abolished by using either apamin combined with charybdotoxin, ouabain plus barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent contractions which were of greater magnitude in arteries denuded of endothelium or in the presence of L-NMMA.In conclusion, the results indicate that in human thyroid arteries the endothelium significantly modulates responses to acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a dominant role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.

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Pore-forming transmembrane domains control ion selectivity and selectivity filter conformation in the KirBac1.1 potassium channel

The Journal of General Physiology ◽

10.1085/jgp.202012683 ◽

2021 ◽

Vol 153 (5) ◽

Author(s):

Marcos Matamoros ◽

Colin G. Nichols

Keyword(s):

Single Molecule ◽

Ion Selectivity ◽

Transmembrane Helix ◽

Selectivity Filter ◽

K Channel ◽

Physical Interaction ◽

Conformationally Constrained ◽

Single Molecule Fret ◽

High K ◽

Low K

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These mutations increase Na+ flux in the absence of K+ and introduce significant proton conductance. Consistent with K+ channel crystal structures, single-molecule FRET experiments show that the SF is conformationally constrained and stable in high-K+ conditions but undergoes transitions to dilated low-FRET states in high-Na+/low-K+ conditions. Relative to wild-type channels, I131M mutants exhibit marked shifts in the K+ and Na+ dependence of SF dynamics to higher K+ and lower Na+ concentrations. These results illuminate the role of I131, and potentially other structural elements outside the SF, in controlling ion selectivity, by suggesting that the physical interaction of these elements with the SF contributes to the relative stability of the constrained K+-induced SF configuration versus nonselective dilated conformations.

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Self-Aligned Solution-Processed Zinc-Tin Oxide Thin-Film Transistors with High-K Solution-Processed Gate Dielectric

MRS Proceedings ◽

10.1557/proc-1247-c06-02 ◽

2010 ◽

Vol 1247 ◽

Author(s):

Chen-Guan Lee ◽

Soumya Dutta ◽

Ananth Dodabalapur

Keyword(s):

Thin Film ◽

Tin Oxide ◽

Thin Film Transistors ◽

Sol Gel ◽

Channel Length ◽

Parasitic Capacitance ◽

Oxide Thin Film ◽

Solution Processed ◽

High K ◽

Zinc Tin Oxide

AbstractWe demonstrate high performance zinc-tin oxide (ZTO) thin-film transistors (TFTs) with low operation voltage, small channel length and low parasitic capacitance. Both the zinc tin oxide and the high-k dielectric, ZrO2, were solution processed by sol-gel methods. A self-aligned process was employed to minimize the parasitic capacitance. The transistors with a channel length of 8 μm operate at 5 V and have a saturation mobility of 2.5 cm2/V·s and an on/off ratio of 5.9×106. Gate-induced surface relief has been found to have strong effect on the performance of the active layer.

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ROMK is required for expression of the 70-pS K channel in the thick ascending limb

AJP Renal Physiology ◽

10.1152/ajprenal.00305.2003 ◽

2004 ◽

Vol 286 (3) ◽

pp. F490-F495 ◽

Cited By ~ 39

Author(s):

Ming Lu ◽

Tong Wang ◽

Qingshang Yan ◽

Wenhui Wang ◽

Gerhard Giebisch ◽

...

Keyword(s):

Functional Expression ◽

Bartter Syndrome ◽

Salt Transport ◽

K Channel ◽

Thick Ascending Limb ◽

Channel Activity ◽

Loss Of Function ◽

High K ◽

Hypokalemic Alkalosis ◽

Severe Reduction

Apical potassium recycling is crucial for salt transport by the thick ascending limb (TAL). Loss-of-function mutations in the K channel, ROMK (Kir1.1; KCNJ1), cause Bartter syndrome, a genetically heterogeneous disorder characterized by severe reduction in salt absorption by the TAL, Na wasting, polyuria, and hypokalemic alkalosis. ROMK(-/-) null mice exhibit a Bartter phenotype and lack the small-conductance (30-pS) apical K channel (SK) in the TAL. However, a distinct 70-pS K channel can also significantly contribute to the apical conductance of TAL. We now examine the effect of ROMK deletion on the functional expression of the 70-pS K channel in the TAL. Functional expression of the 70-pS K channel was low [average channel acitivty ( NPo) = 0.02] in ROMK(+/+) mice on a control K diet but increased to 0.27 by high-K intake for 2 wk. In contrast, the high-K diet decreased NPo of SK by ∼30%, from 2.04 to 1.44. In ROMK heterozygous (+/-) mice on a control K diet, SK activity was about one-half of that observed in ROMK(+/+) mice (0.95 vs. 2.04). The high-K diet also reduced SK activity in ROMK(+/-) mice by ∼40% (from 0.95 to 0.55) but increased NPo of the 70-pS K channel from 0 to 0.09 in ROMK(+/-) mice. This corresponds to ∼30% of channel activity ( NPo = 0.27) observed in ROMK(+/+) mice. Neither the 70-pS nor the 30-pS K channels were observed in TAL cells from ROMK(-/-) mice on either the normal or high-K diets. Thus functional expression of the 70-pS K channel is enhanced by increasing dietary K and requires expression of ROMK. It is likely that ROMK forms a critical subunit of the 70-pS K channel, accounting for the loss of apical K secretory channel activity in ROMK Bartter syndrome.

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