• Title/Summary/Keyword: K^+$ currents

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Imipramine Inhibits A-type Delayed Rectifier and ATP-Sensitive $K^{+}$ Currents Independent of G-Protein and Protein Kinase C in Murine Proximal Colonic Myocytes

  • Choi, Seok;Parajuli, Shankar Prasad;Lim, Geon-Han;Kim, Jin-Ho;Yeum, Cheol-Ho;Yoon, Pyung-Jin;Jun, Jae-Yeoul
    • Archives of Pharmacal Research
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    • v.29 no.11
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    • pp.998-1005
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    • 2006
  • The effects of imipramine on A-type delayed rectifier $K^{+}$ currents and ATP-sensitive $K^{+}\;(K_{ATP)$ currents were studied in isolated murine proximal colonic myocytes using the whole-cell patch-clamp technique. Depolarizing test pulses between-80 mV and +30 mV with 10 mV increments from the holding potential of-80 mV activated voltage-dependent outward $K^{+}$ currents that peaked within 50 ms followed by slow decreasing sustained currents. Early peak currents were inhibited by the application of 4-aminopyridine, whereas sustained currents were inhibited by the application of TEA. The peak amplitude of A-type delayed rectifier $K^{+}$ currents was reduced by external application of imipramine. The half-inactivation potential and the half-recovery time of A-type delayed rectifier $K^{+}$ currents were not changed by imipramine. With 0.1 mM ATP and 140 mM $K^{+}$ in the pipette and 90 mM $K^{+}$ in the bath solution and a holding potential of -80 mV, pinacidil activated inward currents; this effect was blocked by glibenclamide. Imipramine also inhibited $K_{ATP}$ currents. The inhibitory effects of imipramine in A-type delayed rectifier $K^{+}$ currents and $K_{ATP}$ currents were not changed by guanosine 5-O-(2-thiodiphosphate) ($GDP{\beta}S$) and chelerythrine, a protein kinase C inhibitor. These results suggest that imipramine inhibits A-type delayed rectifier $K^{+}$ currents and $K_{ATP}$ currents in a manner independent of G-protein and protein kinase C.

Modulation of Outward Potassium Currents by Nitric Oxide in Longitudinal Smooth Muscle Cells of Guinea-pig Ileum

  • Kwon, Seong-Chun;Rim, Se-Joong;Kang, Bok-Soon
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.225-232
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    • 1998
  • To investigate the possible involvement of outward potassium ($K^+$) currents in nitric oxide-induced relaxation in intestinal smooth muscle, we used whole-cell patch clamp technique in freshly dispersed guinea-pig ileum longitudinal smooth muscle cells. When cells were held at -60 mV and depolarized from -40 mV to -50 mV in 10 mV increments, sustained outward $K^+$ currents were evoked. The outward $K^+$ currents were markedly increased by the addition of 10 ${\mu}M$ sodium nitroprusside (SNP). 10 ${\mu}M$ S-nitroso-N-acetylpenicillamine (SNAP) and 1 mM 8-Bromo-cyclic GMP (8-Br-cGMP) also showed a similar effect to that of SNP. 1 mM tetraethylammonium (TEA) significantly reduced depolarization-activated outward $K^+$ currents. SNP-enhanced outward $K^+$ currents were blocked by the application of TEA. High EGTA containing pipette solution (10 mM) reduced the control currents and also inhibited the SNP-enhanced outward $K^+$ currents. 5 mM 4-aminopyridine (4-AP) significantly reduced the control currents but showed no effect on SNP-enhanced outward $K^+$ currents. 0.3 ${\mu}M$ apamin and 10 ${\mu}M$ glibenclamide showed no effect on SNP-enhanced outward $K^+$ currents. 10 ${\mu}M$ 1H-[1,2,4]oxadiazolo [4,3-a]quinoxaline-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, significantly blocked SNP-enhanced $K^+$ currents. We conclude that NO donors activate the $Ca^{2+}-activated$ $K^+$ channels in guinea-pig ileal smooth muscle via activation of guanylate cyclase.

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The Characteristics of Coastal Currents to the Northwest of the Taean Peninsula in the Yellow Sea (서해 태안반도 북서 연안해역에서의 연안류 특성)

  • Shin, Hong-Ryeol
    • Ocean and Polar Research
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    • v.27 no.4
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    • pp.433-441
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    • 2005
  • To investigate the characteristics of tidal currents and water circulation in the coastal waters off the Taean Peninsula, tidal currents and sea levels were measured at the study area from 1998 to 2004. In the central waterway to the south of Changan Sand Ridge, mean speed of tidal currents and residual currents were 74.0cm/s, 17.8cm/s respectively; the dominant residual currents flowed northeastward, and the amplitudes of semi-diurnal components $(M_2,\;S_2)$ were larger than diurnal components $(O_1,\;K_1)$. The flood and ebb tidal currents were northeastward and southwestward, respectively, and each period was about 6 hours for them, which was consistent with the period of sea levels at the study area. In the coastal region near Hakampo, Taean, mean velocities of tidal currents and residual currents were 46.1cm/s, 30.8cm/s respectively, and the dominant residual currents flowed southwestward. The amplitudes of shallow water constituents $(M_4,\;MS_4)$ were relatively laige, which were weaker to the northeastern coastal region off Mineodo. The northeastward flow continued for about $2{\sim}3$ hours, while the southwestward flow continued for about $9{\sim}10$ hours near Hakampo during the tidal period. Tidal currents flowed northeastward in the central area of the waterway during the period from the Low Water Level (LWL) to the High Water Level (HWL). While the currents in the coastal region flowed northeastward for the first 3 hours after the LWL, southwestward counter-currents flowed between 3 and 6 hours after the LWL. During the period from the HWL to the LWL, the dominant currents flowed southwestward in the study area except to the northeastern coastal region off Mineodo. Along the shorelines, the counter-currents flowed northward between 4 and 6 hours after the HWL. It seems that the counter-currents near the coastal region are caused by the topography and the geography of the shorelines at the study area.

Inhibition of Pacemaker Activity of Interstitial Cells of Cajal by Hydrogen Peroxide via Activating ATP-sensitive $K^+$ Channels

  • Choi Seok;Parajuli Shankar Prasad;Cheong Hyeon-Sook;Paudyal Dilli Parasad;Yeum Cheol-Ho;Yoon Pyung-Jin;Jun Jae-Yeoul
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.1
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    • pp.15-20
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    • 2007
  • To investigate whether hydrogen peroxide($H_2O_2$) affects intestinal motility, pacemaker currents and membrane potential were recorded in cultured interstitial cells of Cajal(ICC) from murine small intestine by using a whole-cell patch clamp. In whole cell patch technique at $30^{\circ}C$, ICC generated spontaneous pacemaker potential under current clamp mode(I=0) and inward currents(pacemaker currents) under voltage clamp mode at a holding potential of -70 mV. When ICC were treated with $H_2O_2$ in ICC, $H_2O_2$ hyperpolarized the membrane potential under currents clamp mode and decreased both the frequency and amplitude of pacemaker currents and increased the resting currents in outward direction under voltage clamp mode. Also, $H_2O_2$ inhibited the pacemaker currents in a dose-dependent manner. Because the properties of $H_2O_2$ action on pacemaker currents were same as the effects of pinacidil(ATP-sensitive $K^+$ channels opener), we tested the effects of glibenclamide(ATP-sensitive $K^+$ channels blocker) on $H_2O_2$ action in ICC, and found that the effects of $H_2O_2$ on pacemaker currents were blocked by co- or pre- treatment of glibenclamide. These results suggest that $H_2O_2$ inhibits pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels.

Nimodipine as a Potential Pharmacological Tool for Characterizing R-Type Calcium Currents

  • Oh, Seog-Bae
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.6
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    • pp.511-519
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    • 2001
  • Nimopidine, one of dihydropyridine derivatives, has been widely used to pharmacologically identify L-type Ca currents. In this study, it was tested if nimodipine is a selective blocker for L-type Ca currents in sensory neurons and heterologous system. In mouse dorsal root ganglion neurons (DRG), low concentrations of nimodipine $(<10\;{\mu}M),$ mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by ${\sim}38%.$ Interestingly, high concentrations of nimodipine $(>10\;{\mu}M)$ further reduced the 'residual' currents in DRG neurons from ${\alpha}_{1E}$ knock-out mice, after blocking L-, N- and P/Q-type Ca currents with $10\;{\mu}M$ nimodipine, $1\;{\mu}M\;{\omega}-conotoxin$ GVIA and 200 nM ${\omega-agatoxin$ IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine $(>10\;{\mu}M)$ also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and ${\alpha}_{1B}\;and\;{\alpha}_{1E}$ subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine $(>10\;{\mu}M)$ is not necessarily selective for L-type Ca currents. While care should be taken in using nimodipine for pharmacologically defining L-type Ca currents from native macroscopic Ca currents, nimodipine $(>10\;{\mu}M)$ could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.

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Field Observations and Hydraulic Model Experiments of Tidal Currents in Chinhae Bay (진해만 조류의 현장관측 및 수리모형실험)

  • CHANG Sun-Duck;KIM Cha-Kyum;LEE Jong-Sup
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.26 no.4
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    • pp.346-352
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    • 1993
  • Tidal currents and tidal residual currents in Chinhae Bay are investigated by the field observations and hydraulic experiments during the spring tide and neap tide. The horizontal and vertical scales of the model are l/2,000 and 1/159, respectively. The hydraulic model results roughly coincide with the field data. Maximum tidal currents during the spring tide and neap tide in the central channel of Chinhae Bay are strong as about 90 and 30cm/s respectively, and strong tidal residual currents take place. Maximum tidal currents during the spring tide and neap tide in the western and northern part of the bay are weak as below 30 and 10cm/s respectively, and also tidal residual currents are weak. Tidal residual currents rotating clockwise occur in the central part of the bay. Northward tidal residual currents in the northern part of Kajo-do are predominant, whereas southward ones in the southern part of Kajo-do are remarkable. The surface currents in the bay depend strongly on the wind and river flow, and it seems to be remarkable during the neap tide.

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Sustained $K^+$ Outward Currents are Sensitive to Intracellular Heteropodatoxin2 in CA1 Neurons of Organotypic Cultured Hippocampi of Rats

  • Jung, Sung-Cherl;Eun, Su-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.5
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    • pp.343-348
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    • 2012
  • Blocking or regulating $K^+$ channels is important for investigating neuronal functions in mammalian brains, because voltage-dependent $K^+$ channels (Kv channels) play roles to regulate membrane excitabilities for synaptic and somatic processings in neurons. Although a number of toxins and chemicals are useful to change gating properties of Kv channels, specific effects of each toxin on a particular Kv subunit have not been sufficiently demonstrated in neurons yet. In this study, we tested electro-physiologically if heteropodatoxin2 ($HpTX_2$), known as one of Kv4-specific toxins, might be effective on various $K^+$ outward currents in CA1 neurons of organotypic hippocampal slices of rats. Using a nucleated-patch technique and a pre-pulse protocol in voltage-clamp mode, total $K^+$ outward currents recorded in the soma of CA1 neurons were separated into two components, transient and sustained currents. The extracellular application of $HpTX_2$ weakly but significantly reduced transient currents. However, when $HpTX_2$ was added to internal solution, the significant reduction of amplitudes were observed in sustained currents but not in transient currents. This indicates the non-specificity of $HpTX_2$ effects on Kv4 family. Compared with the effect of cytosolic 4-AP to block transient currents, it is possible that cytosolic $HpTX_2$ is pharmacologically specific to sustained currents in CA1 neurons. These results suggest that distinctive actions of $HpTX_2$ inside and outside of neurons are very efficient to selectively reduce specific $K^+$ outward currents.

Inhibition of K+ outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week

  • Kang, Shin Wook;Ahn, Ji Woong;Ahn, Seung Cheol
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.251-257
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    • 2017
  • Inhibition of $K^+$ outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) and ICR mice of the same age (postnatal day (P) 0 -P6) were used as controls. Voltage steps from -100 mV to 40 mV elicited small inward currents (-100 mV~-70 mV) and slow rising $K^+$ outward currents (-60 mV~40 mV) which activated near -50 mV in all OHCs tested. Linopirdine, a known blocker of $K^+$ currents activated at negative potentials ($I_{K,n}$), did cause inhibition at varying degree (severe, moderate, mild) in $K^+$ outward currents of heterozygous (+/cir) or homozygous (cir/cir) mice OHCs in the concentration range between 1 and $100{\mu}m$, while it was apparent only in one ICR mice OHC out of nine OHCs at $100{\mu}m$. Although the half inhibition concentrations in heterozygous (+/cir) or homozygous (cir/cir) mice OHCs were close to those reported in $I_{K,n}$, biophysical and pharmacological properties of $K^+$ outward currents, such as the activation close to -50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with $I_{K,n}$ reported in other tissues. Our results show that the delayed rectifier type $K^+$ outward currents, which are not similar to $I_{K,n}$ with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (cir/cir) or heterozygous (+/cir) mice OHCs.

Modeling and Analysis of Leakage Currents in PWM-VSI-Fed PMSM Drives for Air-Conditioners with High Accuracy and within a Wide Frequency Range

  • Sun, Kai;Lu, Yangjun;Xing, Yan;Huang, Lipei
    • Journal of Power Electronics
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    • v.16 no.3
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    • pp.970-981
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    • 2016
  • Leakage currents occur in pulse-width-modulated voltage source inverter (PWM-VSI)-fed permanent magnet synchronous motor (PMSM) drives for air-conditioners, which seriously affect system safety and operation performance. High accuracy modeling and prediction of leakage currents are key issues for the design and implementation of air-conditioning products. In this study, the generation mechanism of leakage currents is discussed. A systematic modeling approach of leakage currents is proposed, including the modeling of leakage current sources and leakage current paths. By using the proposed approach, the complete model of leakage currents in PWM-VSI-fed PMSM drives for air-conditioners has been developed based on the extraction of all parameters. A comparison between the simulated leakage currents based on the developed model and measured leakage currents in the outdoor unit of an air-conditioning product is conducted. The comparison verifies the effectiveness of the proposed modeling approach, and the developed model exhibits high accuracy within a wide frequency range.

A Study of the SPWM High-Frequency Harmonic Circulating Currents in Modular Inverters

  • Xu, Sheng;Ji, Zhendong
    • Journal of Power Electronics
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    • v.16 no.6
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    • pp.2119-2128
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    • 2016
  • Due to detection and control errors, some high-frequency harmonics with voltage-source characteristics cause circulating currents in modular inverters. Moreover, the circulating currents are usually affected by the output filters (OF) of each module due to their filter and resonance properties. The interaction among the circulating currents in the modules increase the power loss and reduce system stability and control precision. Therefore, this paper reports the results of a study on the SPWM high-frequency harmonics circulating currents for a double-module VSI. In the paper, an analysis of the circulating-current circuits is briefly described. Next, a mathematic model of the single-module output voltage based on the carrier frequency of SPWM is built. On this basis, through mathematic modeling of high-frequency harmonic circulating currents, the formation mechanism and distribution characteristics of circular currents and their influences are studied in detail. Finally, the influences of the OF on the circulating currents are studied by mainly taking an LC-type filter as an example. A theoretical analysis and experimental results demonstrate some important characteristics. First, the carrier phase shifting of the SPWM for each module is the major cause of the SPWM harmonic circulating currents, and the circulating currents are in an odd distribution around n-times the carrier frequency $n{\omega}_s$, where n = 1, 2, 3, ${\ldots}$. Second, the harmonic circular currents do not flow into the parallel system. Third, the OF can effectively suppress the non-circulating part of the high-frequency harmonic currents but is ineffective for the circulation part, and actually reduces system stability.