共查询到20条相似文献,搜索用时 10 毫秒
1.
Potassium channels have become a focus in cancer biology as they play roles in cell behaviours associated with cancer progression, including proliferation, migration and apoptosis. Two-pore domain (K2P) potassium channels are background channels which enable the leak of potassium ions from cells. As these channels are open at rest they have a profound effect on cellular membrane potential and subsequently the electrical activity and behaviour of cells in which they are expressed. The K2P family of channels has 15 mammalian members and already 4 members of this family (K2P2.1, K2P3.1, K2P9.1, K2P5.1) have been implicated in cancer. Here we examine the expression of all 15 members of the K2P family of channels in a range of cancer types. This was achieved using the online cancer microarray database, Oncomine (www.oncomine.org). Each gene was examined across 20 cancer types, comparing mRNA expression in cancer to normal tissue. This analysis revealed all but 3 K2P family members (K2P4.1, K2P16.1, K2P18.1) show altered expression in cancer. Overexpression of K2P channels was observed in a range of cancers including breast, leukaemia and lung while more cancers (brain, colorectal, gastrointestinal, kidney, lung, melanoma, oesophageal) showed underexpression of one or more channels. K2P1.1, K2P3.1, K2P12.1, were overexpressed in a range of cancers. While K2P1.1, K2P3.1, K2P5.1, K2P6.1, K2P7.1 and K2P10.1 showed significant underexpression across the cancer types examined. This analysis supports the view that specific K2P channels may play a role in cancer biology. Their altered expression together with their ability to impact the function of other ion channels and their sensitivity to environmental stimuli (pO2, pH, glucose, stretch) makes understanding the role these channels play in cancer of key importance. 相似文献
2.
Xuxia Liu Haixia Huang Wei Wang Jun Wang Frederick Sachs Weizhen Niu 《The Journal of membrane biology》2008,226(1-3):17-25
Stress in the lipids of the cell membrane may be responsible for activating stretch-activated channels (SACs) in nonspecialized sensory cells such as cardiac myocytes, where they are likely to play a role in cardiac mechanoelectric feedback. We examined the influence of the mechanical microenvironment on the gating of stretch-activated potassium channels (SAKCs) in rat atrial myocytes. The goal was to examine the role of the cytoskeleton in the gating process. We recorded from blebs that have minimal cytoskeleton and cells treated with cytochalasin B (cyto-B) to disrupt filamentous actin. Histochemical and electron microscopic techniques confirmed that the bleb membrane was largely free of F-actin. Channel currents showed mechanosensitivity and potassium selectivity and were activated by low pH and arachidonic acid, similar to properties of TREK-1. Some patches showed a time-dependent decrease in current that may be adaptation or inactivation, and since this decrease appeared in control cells and blebs, it is probably not the result of adaptation in the cytoskeleton. Cyto-B treatment and blebbing caused an increase in background channel activity, suggesting a transfer of stress from actin to bilayer and then to the channel. The slope sensitivity of gating before and after cyto-B treatment was similar to that of blebs, implying the characteristic change of dimensions associated with channel gating was the same in the three mechanical environments. The mechanosensitivity of SAKCs appears to be the result of interaction with membrane lipids and not of direct involvement of the cytoskeleton. 相似文献
3.
目的:研究Kv1.3钾离子通道在SKOV3卵巢癌细胞中的表达及其在细胞增殖和细胞周期中的作用。方法:应用RT—PCR和免疫细胞化学鉴别Kv1.3钾离子通道在SKOV3卵巢癌细胞中的表达。应用MTT和流式细胞技术观察KV1.3钾离子通道对SKOV3卵巢癌细胞增殖及细胞周期的影响。结果:4-氨基吡啶是Kv1.3钾离子通道特异性阻滞剂。不同浓度的4-氨基吡啶可以明显抑制SKOV3细胞的增殖,并且细胞周期也受到影响。G0/G1细胞比例增加,S期和G2/M期细胞比例下降。结论:Kv1.3钾离子通道在SKOV3卵巢癌细胞中表达,并且在细胞增殖及细胞周期变换中扮演着重要的角色。 相似文献
4.
瓮占平王纯陶红宁辉纪向虹 《现代生物医学进展》2011,11(11):2053-2057
目的:研究Kv1.3钾离子通道在SKOV3卵巢癌细胞中的表达及其在细胞增殖和细胞周期中的作用。方法:应用RT-PCR和免疫细胞化学鉴别Kv1.3钾离子通道在SKOV3卵巢癌细胞中的表达。应用MTT和流式细胞技术观察KV1.3钾离子通道对SKOV3卵巢癌细胞增殖及细胞周期的影响。结果:4-氨基吡啶是Kv1.3钾离子通道特异性阻滞剂。不同浓度的4-氨基吡啶可以明显抑制SKOV3细胞的增殖,并且细胞周期也受到影响。G0/G1细胞比例增加,S期和G2/M期细胞比例下降。结论:Kv1.3钾离子通道在SKOV3卵巢癌细胞中表达,并且在细胞增殖及细胞周期变换中扮演着重要的角色。 相似文献
5.
Yangyang Yan Youshan Yang Shumin Bian Fred J. Sigworth 《The Journal of membrane biology》2012,245(11):667-674
The slack (slo2.2) gene codes for a potassium-channel α-subunit of the 6TM voltage-gated channel family. Expression of slack results in Na+-activated potassium channel activity in various cell types. We describe the purification and reconstitution of Slack protein and show that the Slack α-subunit alone is sufficient for potassium channel activity activated by sodium ions as assayed in planar bilayer membranes and in membrane vesicles. 相似文献
6.
7.
Immunofluorescence and immunogold techniques were used to determine the presence and distribution of aquaporin-1 (AQP1) within the rat uterus. Uterine tissue from non-pregnant (proestrus) as well as pregnant (days 1, 3, 6 and 7) rats were used. It was found that this water channel was present in the myometrium of the pregnant rat uterus with the intensity of AQP1 immunoreactivity increasing from day 1 to day 6 of pregnancy. In particular, an increase was also observed in mesometrial as compared to antimesometrial myometrium. Immunolocalization at the electron microscope level indicated that AQP1 was localized to the plasma membrane of smooth muscle cells found within the inner circular layer. It is suggested that AQP1 plays a role in stromal oedema, uterine closure and orientation of the blastocyst. 相似文献
8.
Lotshaw DP 《The Journal of membrane biology》2006,210(1):51-70
Multiple genes of the TASK subfamily of two-pore domain K+ channels are reported to be expressed in rat glomerulosa cells. To determine which TASK isoforms contribute to native leak
channels controlling resting membrane potential, patch-clamp studies were performed to identify biophysical and pharmacological
characteristics of macroscopic and unitary K+ currents diagnostic of recombinant TASK channel isoforms. Results indicate K+ conductance (gK+) is mediated almost exclusively by a weakly voltage-dependent (leak) K+ channel closely resembling TASK-3. Leak channels exhibited a unitary conductance approximating that expected for TASK-3 under
the recording conditions employed, brief mean open times and a voltage-dependent open probability. Extracellular H+ induced voltage-independent inhibition of gK+, exhibiting an IC50 of 56 nM (pH 7.25) and a Hill coefficient of 0.75. Protons inhibited leak channel open probability (Po) by promoting a long-lived closed state (τ > 500 ms). Extracellular Zn2+ mimicked the effects of H+; inhibition of gK+ exhibited an IC50 of 41 μM with a Hill coefficient of 1.26, inhibiting channel gating by promoting a long-lived closed state. Ruthenium red (5 μM) inhibited gK+ by 75.6% at 0 mV. Extracellular Mg2+ induced voltage-dependent block of gK+, inhibiting unitary current amplitude without affecting mean open time. Bupivacaine induced voltage-dependent block of gK+, exhibiting IC50 values of 116 μM at −100 mV and 28 μM at 40 mV with Hill coefficients of 1 at both potentials. Halothane induced a voltage-independent stimulation of gK+ primarily by decreasing the leak channel closed-state dwell time. 相似文献
9.
In the present study, the whole-cell patch-clamp technique was applied to follow the inhibitory effect of genistein — a tyrosine
kinase inhibitor and a natural anticancer agent—on the activity of voltage-gated potassium channels Kv1.3 expressed in human
T lymphocytes (TL). Obtained data provide evidence that genistein application in the concentration range of 1–80 μM reversibly decreased the whole-cell potassium currents in TL in a concentration-dependent manner to about 0.23 of the control
value. The half-blocking concentration range of genistein was from 10 to 40 μM. The current inhibition was correlated in time with a significant decrease of the current activation rate. The steady-state
activation of the currents was unchanged upon application of genistein, as was the inactivation rate. The inhibitory effect
of genistein on the current amplitude and activation kinetics was voltage-independent. The current inhibition was not changed
significantly in the presence of 1 mM of sodium orthovanadate, a tyrosine phosphatase inhibitor. Application of daidzein, an inactive genistein analogue, did not
affect significantly either the current amplitudes or the activation kinetics. Possible mechanisms of the observed phenomena
and their significance for genistein-induced inhibition of cancer cell proliferation are discussed. 相似文献
10.
These experiments were conducted to determine the membrane K+ currents and channels in human urinary bladder (HTB-9) carcinoma cells in vitro. K+ currents and channel activity were assessed by the whole-cell voltage clamp and by either inside-out or outside-out patch
clamp recordings. Cell depolarization resulted in activation of a Ca2+-dependent outward K+ current, 0.57 ± 0.13 nS/pF at −70 mV holding potential and 3.10 ± 0.15 nS/pF at 30 mV holding potential. Corresponding patch
clamp measurements demonstrated a Ca2+-activated, voltage-dependent K+ channel (KCa) of 214 ± 3.0 pS. Scorpion venom peptides, charybdotoxin (ChTx) and iberiotoxin (IbTx), inhibited both the activated current
and the KCa activity. In addition, on-cell patch recordings demonstrated an inwardly rectifying K+ channel, 21 ± 1 pS at positive transmembrane potential (V
m
) and 145 ± 13 pS at negative V
m
. Glibenclamide (50 μm), Ba2+ (1 mm) and quinine (100 μm) each inhibited the corresponding nonactivated, basal whole-cell current. Moreover, glibenclamide inhibited K+ channels in inside/out patches in a dose-dependent manner, and the IC50= 46 μm. The identity of this K+ channel with an ATP-sensitive K+ channel (KATP) was confirmed by its inhibition with ATP (2 mm) and by its activation with diazoxide (100 μm). We conclude that plasma membranes of HTB-9 cells contain the KCa and a lower conductance K+ channel with properties consistent with a sulfonylurea receptor-linked KATP.
Received: 12 June 1997/Revised: 21 October 1997 相似文献
11.
R. Wondergem M. Cregan L. Strickler R. Miller J. Suttles 《The Journal of membrane biology》1998,161(3):257-262
These experiments were done to determine the effect of glibenclamide and diazoxide on the growth of human bladder carcinoma
(HTB-9) cells in vitro. Cell growth was assayed by cell counts, protein accumulation, and 3H-thymidine uptake. Glibenclamide added at 75 and 150 μm for 48 hr reduced cell proliferation. Dose-inhibition curves showed that glibenclamide added for 48 hr reduced cell growth
at concentrations as low as 1 μm (IC50= 73 μm) when growth was assayed in the absence of added serum. This μM-effect on cell growth was in agreement with the dose range
in which glibenclamide decreased open probability of membrane KATP channels. Addition of glibenclamide for 48 hr also altered the distribution of cells within stages of the cell cycle as determined
by flow cytometry using 10−5
m bromodeoxyuridine. Glibenclamide (100 μm) increased the percentage of cells in G0/G1 from 33.6% (vehicle control) to 38.3% (P < 0.05), and it reduced the percentage of cells in S phase from 38.3% to 30.6%. On the other hand, diazoxide, which opens
membrane KATP channels in HTB-9 cells, stimulated growth measured by protein accumulation, but it did not increase the cell number. We
conclude that the sulfonylurea receptor and the corresponding membrane KATP channel are involved in mechanisms controlling HTB-9 cell growth. However, KATP is not rate-limiting among the signaling mechanisms or molecular switches that regulate the cell cycle.
Received: 12 June 1997/Revised: 21 October 1997 相似文献
12.
The whole-cell patch-clamp technique was applied to study the modulatory effect of resveratrol on voltage-gated potassium
channel Kv1.3 expressed in human lymphocytes. Results demonstrate that application of resveratrol in the concentration range
1–200 μM inhibited the channel activity in a concentration-dependent manner to about 18% of the control value. The half-blocking concentration
of resveratrol was 40.9 μM, whereas the Hill coefficient was 1.05. The inhibition was time-dependent and slowly reversible. The inhibitory effect of
resveratrol was correlated in time with a significant slowing of the current activation, whereas the inactivation rate remained
unaffected upon application of resveratrol. The inhibition of Kv1.3 channels was voltage-independent. The steady-state activation
of the currents remained unchanged upon resveratrol application. The magnitude of the inhibitory effect of resveratrol was
not altered when resveratrol was coapplied with genistein. The possible mechanism of the inhibitory effect and its significance
for biological activity of resveratrol are discussed. 相似文献
13.
Zhong-Wei Liu Xiao-Lin Niu Kun-Lun Chen Yu-Jie Xing Xuan Wang Chuan Qiu Deng-Feng Gao 《Biological trace element research》2013,153(1-3):220-228
The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study. Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically. Expression of ATP-sensitive potassium channels (KATP) subunits—SUR2A and Kir6.2—were examined by real-time PCR and Western blotting. The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, it is novel for us to find down-regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac KATP gene expression was identified after co-administration of ADR and Se deficiency. Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression. These results indicate that decreased expression of cardiac KATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of KATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring KATP expression, showing potential clinical application in cancer chemotherapy. 相似文献
14.
Janice L. Robertson Lawrence G. Palmer Benoît Roux 《The Journal of general physiology》2008,132(6):613-632
Inward-rectifier potassium (Kir) channels differ from the canonical K+ channel structure in that they possess a long extended pore (~85 Å) for ion conduction that reaches deeply into the cytoplasm. This unique structural feature is presumably involved in regulating functional properties specific to Kir channels, such as conductance, rectification block, and ligand-dependent gating. To elucidate the underpinnings of these functional roles, we examine the electrostatics of an ion along this extended pore. Homology models are constructed based on the open-state model of KirBac1.1 for four mammalian Kir channels: Kir1.1/ROMK, Kir2.1/IRK, Kir3.1/GIRK, and Kir6.2/KATP. By solving the Poisson-Boltzmann equation, the electrostatic free energy of a K+ ion is determined along each pore, revealing that mammalian Kir channels provide a favorable environment for cations and suggesting the existence of high-density regions in the cytoplasmic domain and cavity. The contribution from the reaction field (the self-energy arising from the dielectric polarization induced by the ion's charge in the complex geometry of the pore) is unfavorable inside the long pore. However, this is well compensated by the electrostatic interaction with the static field arising from the protein charges and shielded by the dielectric surrounding. Decomposition of the static field provides a list of residues that display remarkable correspondence with existing mutagenesis data identifying amino acids that affect conduction and rectification. Many of these residues demonstrate interactions with the ion over long distances, up to 40 Å, suggesting that mutations potentially affect ion or blocker energetics over the entire pore. These results provide a foundation for understanding ion interactions in Kir channels and extend to the study of ion permeation, block, and gating in long, cation-specific pores. 相似文献
15.
Maria Micaela Molina-Navarro Esther Roselló-Lletí Ana Ortega Estefanía Tarazón Manuel Otero Luis Martínez-Dolz Francisca Lago José Ramón González-Juanatey Francisco Espa?a Pablo García-Pavía José Anastasio Montero Manuel Portolés Miguel Rivera 《PloS one》2013,8(12)
Background
Dilated cardiomyopathy (DCM) is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function.Methods and Results
Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT). The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples) validated the gene expression of SCN2B (p < 0.0001), KCNJ5 (p < 0.05), KCNJ8 (p < 0.05), CLIC2 (p < 0.05), and CACNB2 (p < 0.05). Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work.Conclusion
This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches. 相似文献16.
Role of Voltage-gated Potassium Channels in Cancer 总被引:3,自引:0,他引:3
Pardo LA Contreras-Jurado C Zientkowska M Alves F Stühmer W 《The Journal of membrane biology》2005,205(3):115-124
Ion channels are being associated with a growing number of diseases including cancer. This overview summarizes data on voltage-gated
potassium channels (VGKCs) that exhibit oncogenic properties: ether-à-go-go type 1 (Eag1). Normally, Eag1 is expressed almost
exclusively in tissue of neural origin, but its ectopic expression leads to uncontrolled proliferation, while inhibition of
Eag1 expression produces a concomitant reduction in proliferation. Specific monoclonal antibodies against Eag1 recognize an
epitope in over 80% of human tumors of diverse origins, endowing it with diagnostic and therapeutic potential. Eag1 also possesses
unique electrophysiological properties that simplify its identification. This is particularly important, as specific blockers
of Eag1 currents are not available. Molecular imaging of Eag1 in live tumor models has been accomplished with dye-tagged antibodies
using 3-D imaging techniques in the near-infrared spectral range.
Abbreviations: EAG: Ether-à-go-go, VGKCs: voltage-gated potassium channels 相似文献
17.
The presence of Kv1.3 voltage-gated potassium channels in rat and human prostate epithelial cells has been previously reported.
We examined, by immunohistochemistry, Kv1.3 levels in 10 normal human prostate, 18 benign prostatic hyperplasia (BPH) and
147 primary human prostate cancer (Pca) specimens. We found high epithelial expression of Kv1.3 in all normal prostate, 16
BPH and 77 (52%) Pca specimens. Compared to normal, Kv1.3 levels were reduced in 1 (6%) BPH specimen and in 70 (48%) Pca specimens.
We found a significant inverse correlation between Kv1.3 levels and tumor grade (r = −0.25, P = 0.003) as well as tumor stage (r = −0.27, P = 0.001). Study of an additional 30 primary Pca specimens showed that 15 (50%) had reduced Kv1.3 immunostaining compared
to matched normal prostate tissue. Our data suggest that in Pca reduced Kv1.3 expression occurs frequently and may be associated
with a poor outcome. 相似文献
18.
19.
Expressed in Xenopus oocytes, KvLQT1 channel subunits yield a small, rapidly activating, voltage- dependent potassium conductance. When coexpressed with the minK gene product, a slowly activating and much larger potassium current results. Using fluctuation analysis and single-channel recordings, we have studied the currents formed by human KvLQT1 subunits alone and in conjunction with human or rat minK subunits. With low external K+, the single-channel conductances of these three channel types are estimated to be 0.7, 4.5, and 6.5 pS, respectively, based on noise analysis at 20 kHz bandwidth of currents at +50 mV. Power spectra computed over the range 0.1 Hz–20 kHz show a weak frequency dependence, consistent with current interruptions occurring on a broad range of time scales. The broad spectrum causes the apparent single-channel current value to depend on the bandwidth of the recording, and is mirrored in very “flickery” single-channel events of the channels from coexpressed KvLQT1 and human minK subunits. The increase in macroscopic current due to the presence of the minK subunit is accounted for by the increased apparent single-channel conductance it confers on the expressed channels. The rat minK subunit also confers the property that the outward single-channel current is increased by external potassium ions. 相似文献
20.
In leech P neurons the inhibition of the Na+-K+ pump by ouabain or omission of bath K+ leaves the membrane potential unaffected for a prolonged period or even induces a marked membrane hyperpolarization, although
the concentration gradients for K+ and Na+ are attenuated substantially. As shown previously, this stabilization of the membrane potential is caused by an increase
in the K+ conductance of the plasma membrane, which compensates for the reduction of the K+ gradient. The data presented here strongly suggest that the increased K+ conductance is due to Na+-activated K+ (KNa) channels. Specifically, an increase in the cytosolic Na+ concentration ([Na+]i) was paralleled by a membrane hyperpolarization, a decrease in the input resistance (Rin) of the cells, and by the occurrence of an outwardly directed membrane current. The relationship between Rin and [Na+]i followed a simple model in which the Rin decrease was attributed to K+ channels that are activated by the binding of three Na+ ions, with half-maximal activation at [Na+]i between 45 and 70 mM. At maximum channel activation, Rin was reduced by more than 90%, suggesting a significant contribution of the KNa channels to the physiological functioning of the cells, although evidence for such a contribution is still lacking. Injection
experiments showed that the KNa channels in leech P neurons are also activated by Li+. 相似文献