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PubMed2004

Enhancement of acetaminophen cytotoxicity in selenium-binding protein-overexpressed COS-1 cells.

The role of selenium-binding protein (SeBP), which has a high ability to associate with acetaminophen (AAP), on the cytotoxicity of AAP was studied. To clarify this issue, we examined the cytotoxic effect of AAP using COS cells stably expressing SeBP. Expression of SeBP enhanced the susceptibility of the cells to AAP-induced cytotoxicity. Several clones of SeBP-expressed COS cells were obtained, and they exhibited different degrees of susceptibility toward AAP. It was found that there is an inverse correlation between the expression level and the cell viability (r=-0.872). On the other hand, no increase in toxicity was observed in the SeBP-expressed cells treated with N-acetyl-p-quinone imine (NAPQI), which is an active metabolite of AAP. These results show that SeBP is an important factor in AAP hepatotoxicity. Moreover, our data suggest that the toxic mechanism of AAP differs from that of NAPQI.

Acetaminophen↗
PubMed1996

Eukaryotic expression systems: a comparison.

Eukaryotic expression systems are frequently employed for the production of recombinant proteins as therapeutics as well as research tools. Most commonly used expression systems are based on stably transfected adherent CHO cells or nonadherent lymphoid cell lines. An efficient alternative is the infection of insect cells by recombinant baculoviruses. Transient expression in mammalian cells, e.g., COS cells, is often used for the production of smaller quantities of proteins. The choice of a suitable expression system depends largely on the biochemical and biological properties of the protein of interest, as well as on the nature of the planned experiments and the amount of recombinant protein required. We summarize here the expression of the cytokine human Leukemia Inhibitory Factor (hu-LIF) in five of the most commonly used systems, namely in CHO, Sp2/0, MEL, COS, and insect cells, in conjunction with an outline of the principles and characteristics of each of these expression systems. In result, the stably transfected cell lines, CHO, Sp2/0, and MEL cells, gave rise to production of fully glycosylated hu-LIF at variable product titers; incompletely glycosylated, albeit biological action hu-LIF could be rapidly produced by transient expression in COS cells or by baculovirus-mediated infection of insect cells.

Animals↗
PubMed2005

Vertebrate nonmuscle myosin II isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis.

RNA interference (RNAi) treatment of monkey COS-7 cells, a cell line that lacks nonmuscle myosin heavy chain II-A (NMHC II-A) but contains NMHC II-B and II-C, was used to investigate the participation of NMHC isoforms in cytokinesis. We specifically suppressed the expression of NMHC II-B or II-C using 21 nucleotide small interfering RNA (siRNA) duplexes. Down-regulation of NMHC II-B protein expression to 10.2 +/- 0.7% inhibited COS-7 cell proliferation by 50% in the RNAi-treated cells compared with control cells. Moreover, whereas 8.7 +/- 1.0% of control cells were multinucleated, 62.4 +/- 8.8% of the NMHC II-B RNAi-treated cells were multinucleated 72 h after transfection. The RNAi-treated cells had increased surface areas and, unlike control cells, lacked actin stress fibers. Treatment of the COS-7 cells with NMHC II-C siRNA decreased NMHC II-C expression to 5.2 +/- 0.1% compared with the endogenous content of II-C; however, down-regulation of NMHC II-C did not cause increased multinucleation. Immunoblot analysis using a pan-myosin antibody showed that the content of NMHC II-C was less than one-twentieth the amount of NMHC II-B, thereby explaining the lack of response to II-C siRNA. Introducing green fluorescent protein (GFP)-tagged NMHC II isoforms into II-B siRNA-treated cells resulted in reduction of multinucleation from 62.4 +/- 8.8% to 17.8 +/- 2.2% using GFP-NMHC II-B, to 29.8 +/- 7.4% using GFP-NMHC II-A, and to 34.1 +/- 8.6% using NMHC II-C-GFP. These studies have shown that expression of endogenous NMHC II-C in COS-7 cells is insufficient for normal cytokinesis and that exogenous NMHC II-A and NMHC II-C can, at least partially, rescue the defect in cytokinesis due to the loss of NMHC II-B.

Actins↗
PubMed2003

Long-term interactions between opioid and cannabinoid agonists at the cellular level: cross-desensitization and downregulation.

In the present study we investigated long-term interactions between opioid and cannabinoid drugs at several steps along their cellular signal transduction pathways. For this purpose we co-transfected HEK-293 and COS-7 cells with delta-opioid (DOR) and CB1-cannabinoid receptors, and examined the effect of prolonged exposure to either opioid (etorphine) or cannabinoid (DALN) agonists on DOR and CB-1 receptor density and on the ability of subsequent application of the agonists to activate G-proteins (as measured by [35S]GTPgammaS binding) and to inhibit cAMP production. In HEK-293 cells, etorphine induced both homologous and heterologous desensitization, while DALN induced only homologous desensitization. This asymmetric cross-desensitization coincided with asymmetric cross downregulation: etorphine downregulated the binding of the cannabinoid ligand [3H]CP55,940, while DALN failed to reduce the binding of the opioid ligand [3H]diprenorphine. In contrast to the asymmetric desensitization in HEK-293 cells, COS-7 cells presented a two-way cross-desensitization between opioid and cannabinoid agonists, and DALN downregulated the binding of [3H]diprenorphine in these cells. Thus, a complete correlation was found between downregulation and reduction in cell responsiveness ('desensitization'). Moreover, when opioid downregulation in HEK-293 cells was inhibited by either hypertonic sucrose solution or protein kinase inhibitors, desensitization was suppressed to the same extent. These results suggest that, under the present experimental conditions, the reduction in cell responsiveness resulted primarily from downregulation of the receptors.

Animals↗
PubMed2002

Characterization of the novel human transmembrane protein 9 (TMEM9) that localizes to lysosomes and late endosomes.

We have identified and characterized the novel human transmembrane protein 9 (TMEM9). TMEM9 encodes a 183 amino-acid protein that contains an N-terminal signal peptide, a single transmembrane region, three potential N-glycosylation sites, and three conserved cys-rich domains in the N-terminus, but no hitherto known functional domains. The protein is highly conserved between species from Caenorhabditis elegans to man and belongs to a novel family of transmembrane proteins. The TMEM9 gene consists of at least 6 exons and is localized to chromosome 1q41. TMEM9 mRNA is expressed in a wide range of tissues and cells. COS-1 cells transfected with a TMEM9 expression plasmid gave three bands of about 28, 31, and 33kDa representing glycosylated forms of TMEM9 with a protein backbone of about 26kDa. In COS-1 cells transfected with a TMEM9-GFP expression construct,TMEM9-GFP is co-expressed with LAMP1 on late endosomes and lysosomes as well as on ER. Thus, TMEM9 is a phylogenetically conserved, widely expressed transmembrane protein with a potential, but unknown function in intracellular transport.

Amino Acid Sequence↗
PubMed1998

Myosin Va associates with microtubule-rich domains in both interphase and dividing cells.

Class V unconventional myosins are two-headed, nonfilamentous, actin-based mechanoenzymes that appear to be expressed ubiquitously. Mice possess at least two myosin V heavy chain genes (dilute and myr6) whose approximately 190 kDa protein products are referred to as myosin Va and Vb, respectively. Using antibodies that are specific for the Va isoform and immunofluorescence microscopy, we show here that myosin Va localizes to the microtubule organizing center (MTOC) in interphase cells, and to the mitotic asters, spindle, and midbody of dividing cells. These associations, which in the case of mitotic cells are characterized by the concentration of myosin Va in the immediate vicinity of the microtubules, were observed in a variety of cell types, including primary and immortal mouse melanocytes and fibroblasts, Hela cells, and Cos cells. Importantly, these associations were not observed in melanocytes and fibroblasts cultured from dilute null mice, indicating that the staining of these microtubule-rich domains was due to the presence of myosin Va, as opposed to another protein(s) containing a shared epitope(s) with myosin Va. When cells were extracted with detergent prior to fixation, myosin Va remained associated with each of these microtubule-rich domains, suggesting that these associations are not due to the possible presence of membranes at these sites. This fact, and our observation that these microtubule-rich domains contain little if any F-actin (based on phalloidin staining), suggest that myosin Va may bind to microtubules either directly or through a microtubule-associated protein. Finally, we found that dilute null fibroblasts in primary culture are twice as likely to be binucleate as wild type fibroblasts of the same genetic background (35% vs. 17%). Together, these results indicate that myosin Va associates with microtubule-rich domains in both interphase and dividing cells, and plays a role in the efficiency of cell division in culture.

3T3 Cells↗
PubMed1996

Steroidogenic factor 1-dependent promoter activity of the human steroidogenic acute regulatory protein (StAR) gene.

Steroidogenic acute regulatory protein (StAR) is required for efficient adrenal cortical and gonadal but not trophoblast steroid hormone synthesis. StAR gene expression in gonadal cells is stimulated by tropic hormones acting through the intermediacy of cAMP. DNA sequence analysis of the human StAR gene promoter revealed two motifs resembling binding sites for steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor transcription factor family that controls expression of steroidogenic hydroxylases. The 5'-most sequence (distal site) is a consensus SF-1 binding site. The proximal site is a consensus estrogen receptor binding half-site. The StAR gene promoter is not active in BeWo choriocarcinoma cells, COS-1 cells, HeLa cells, or SK-OV-3 ovarian adenocarcinoma cells, all of which do not express significant levels of SF-1 mRNA. Introduction of SF-1 into these cells stimulated StAR promoter activity, particularly in response to cAMP. Two orphan nuclear transcription factors that bind to sequences similar to SF-1 sites, NGFI-B/Nur77 and RNR-1, did not support cAMP-stimulated StAR promoter activity in BeWo cells. Mutation of the distal putative SF-1 binding site reduced basal and cAMP-stimulated promoter activity in BeWo cells by 82% and 71%, respectively. Mutation of the proximal putative SF-1 binding site reduced basal and cAMP-stimulated promoter activity by 89% and 96%, respectively. Mutations in both sites reduced basal promoter activity to 7% of wild type promoter activity and cAMP-stimulated promoter activity to less than 5% of the wild type. Deletion analyses of promoter activity were consistent with the mutation studies. Electrophoretic mobility shift assays (EMSAs) demonstrated that the distal site binds to SF-1 expressed in COS-1 cells and to an SF-1-GST fusion protein with high affinity, but that the mutated distal sequence does not. An anti-SF-1 antibody ablated the characteristic SF-1-DNA complex with the distal sequence. The proximal site formed a number of protein-DNA complexes with COS-1 cell extracts, but appeared to have at best only very modest affinity for SF-1. Collectively, our findings demonstrate that SF-1 plays a key role in controlling the basal and cAMP-stimulated expression of the StAR gene. SF-1 can function at two distinct sites in the human StAR gene promoter, apparently by two different types of interaction, to control transcription.

Base Sequence↗
PubMed1985

Homologous recombination between a defective virus and a chromosomal sequence in mammalian cells.

Replacement of the early region of simian virus 40 results in virus that cannot replicate in a normal host, CV-1 cells, but can replicate in COS cells, a derivative of CV-1 cells that constitutively express simian virus 40 tumor antigen (T antigen). However, passage of such an early replacement simian virus 40 mutant in COS cells results in the emergence of virus that can propagate in CV-1 cells. Analysis of this virus revealed that the mutant rescued the integrated T-antigen gene from the COS cell genome. Comparison of the sequence of the recovered virus with that of the viral DNA resident in COS cells (strain 776) and the mutant used in our studies (derived from strain 777) proves that the mutant virus acquired the T-antigen gene from the COS cell chromosome via homologous recombination. Most probably this process was mediated by a direct genetic exchange.

Amino Acid Sequence↗
PubMed2001

Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain.

Interleukin (IL)-13 receptor alpha2 (IL-13Ralpha2) chain is an essential binding component for IL-13-mediated ligand binding. Recently, we have demonstrated that this receptor chain also plays an important role in the internalization of IL-13. To study the mechanism of IL-13 internalization, we generated mutated IL-13Ralpha2 chains that targeted trileucine residues (Leu(335), Leu(336), and Leu(337)) in the transmembrane domain and a tyrosine motif (Tyr(343)) in the intracellular domain and transfected these cDNAs in COS-7 cells. Cells that expressed a C-terminally truncated IL-13Ralpha2 chain (Delta335) did not bind IL-13, suggesting that the trileucine region modulates IL-13 binding. Truncation of IL-13Ralpha2 chain with a mutation in the trileucine region resulted in significantly decreased internalization compared with wild type IL-13Ralpha2 chain transfected cells. COS-7 cells transfected with tyrosine motif mutants exhibited a similar internalization level compared with wild type IL-13Ralpha2 chain transfected cells; however, dissociation of cell surface IL-13 was faster compared with wild type IL-13Ralpha2 transfectants. These results were further confirmed by determining the cytotoxicity of a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE38QQR) to cells that expressed IL-13Ralpha2 chain mutants. We further demonstrate that the IL-13Ralpha2 chain is not ubiquitinated and that internalization of IL-13Ralpha2 did not depend on ubiquitination. Together, our findings suggest that the dileucine motif in the trileucine region and tyrosine motif participate in IL-13Ralpha2 internalization in distinct manners.

ADP Ribose Transferases↗
PubMed2005

SLC5A9/SGLT4, a new Na+-dependent glucose transporter, is an essential transporter for mannose, 1,5-anhydro-D-glucitol, and fructose.

We isolated a cDNA clone of SLC5A9/SGLT4 from human small intestinal full-length cDNA libraries, and functionally characterized it in vitro. The messenger RNA encoding SGLT4 was mainly expressed in the small intestine and kidney, among the human tissues tested. COS-7 cells transiently expressing SGLT4 exhibited Na(+)-dependent alpha-methyl-D-glucopyranoside (AMG) transport activity with an apparent K(m) of 2.6 mM, suggesting that SGLT4 is a low affinity-type transporter. The rank order of naturally occurring sugar analogs for the inhibition of AMG transport was: D-mannose (Man) >> D-glucose (Glc) > D-fructose (Fru) = 1,5-anhydro-D-glucitol (1,5AG) > D-galactose (Gal). Recognition of Man as a substrate was confirmed by direct uptake of Man into the cell. COS-7 cells expressing a putative murine SGLT4 ortholog showed similar Na(+)-dependent AMG transport activity and a similar deduced substrate specificity. These results suggest that SGLT4 would have unique physiological functions (i.e., absorption and/or reabsorption of Man, 1,5AG, and Fru, in addition to Glc).

Amino Acid Sequence↗
PubMed1996

Molecular basis for erythrocyte Le(a+ b+) and salivary ABH partial-secretor phenotypes: expression of a FUT2 secretor allele with an A-->T mutation at nucleotide 385 correlates with reduced alpha(1,2) fucosyltransferase activity.

The SewA385T mutation of the FUT2 gene was found to correlate with both the erthrocyte Le(a + b+) and/or salivary ABH partial-secretor phenotypes of Polynesians. Constructs with FUT1 and FUT2 wild type genes, and the FUT2 SewA385T, seG428A and seC571T mutated alleles, were cloned into pcDNAI, and expressed in COS-7 cells. COS-7 cells transfected with the SewA385T allele had weak, but detectable, alpha(1,2)fucosyltransferase activity, with an acceptor substrate pattern similar to the wild type FUT2 gene. Comparative kinetic studies from cell extracts with mutated SewA385T and wild type FUT2 alleles gave similar Km values, but less enzyme activity was present in cells transfected with SewA385T (Vmax 230 pmol h-1 mg-1), as compared to those transfected with FUT2 (Vmax 1030 pmol h-1 mg-1), suggesting that the mutated enzyme is more unstable. These results confirm that the molecular basis for the erythrocyte Le(a + b+), and the associated ABH salivary partial-secretor phenotype, is an amino acid change of Ile129-->Phe in the secretor alpha(1,2)fucosyltransferase.

ABO Blood-Group System↗
PubMed1999

Intracellular amyloidogenesis by human islet amyloid polypeptide induces apoptosis in COS-1 cells.

Human islet amyloid polypeptide (hIAPP) is co-secreted with insulin from pancreatic islet beta cells. This peptide spontaneously aggregates in the form of fibrils, and amyloid deposits are associated with dead or degenerating beta cells, a hallmark of noninsulin-dependent diabetes mellitus. We demonstrated that COS-1 cells transfected with vectors expressing hIAPP exhibited intracellular amyloid deposits that were associated with cell death (O'Brien, Butler, Kreutter, Kane, Eberhardt, Am J Pathol 1995, 147:609-616). To establish the mechanism of cell death, we transfected COS-1 cells with vectors expressing amyloidogenic hIAPP or nonamyloidogenic rat IAPP and mutant hIAPP constructs and assayed them for markers characteristic of apoptosis and necrosis by fluorescence-activated cell sorting analysis. Amyloidogenic hIAPP-transfected COS cells contained up to threefold more apoptotic cells present at 96 hours after transfection compared with the nonamyloidogenic vector controls. The hIAPP-induced apoptosis was negligible at 24 and 48 hours after transfection and was maximal at 96 hours which parallels the time course of amyloidogenesis. Immunohistochemical staining and confocal microscopy showed that hIAPP is localized with distinct clustering in the endoplasmic reticulum and Golgi apparatus with no discernable extracellular staining. These experiments provide direct evidence that intracellular hIAPP amyloid causes cell death by triggering apoptotic pathways.

Amyloid↗
PubMedDate not supplied

Expression pattern of nuclear p53 is unique in COS-1 cells.

As p53 is transcriptionally inactive in COS-1 cells, we felt it would be interesting to study the relative time course of expression of nuclear p53 and the onset of S phase. Our results indicated that the expression of nuclear p53 lagged behind the onset of S phase in COS-1 cells. In addition, rapid nuclear expression of p53, probably resulting from nuclear translocation, occurred immediately after the addition of serum into COS1 cells. No such phenomena were found in B104-1 and BHK cells.

Animals↗
PubMed1998

Incorporation of leucocyte GPI-anchored proteins and protein tyrosine kinases into lipid-rich membrane domains of COS-7 cells.

Several human leucocyte surface glycoproteins and two lymphoid protein kinases were transiently expressed in monkey COS-7 fibroblastoid cells. All glycosylphospha-tidylinositol (GPI)-anchored proteins (CD14, CD16B, CD48, CD59, CD87 and GPI-anchored versions of CD2 and CD25) and protein tyrosine kinase (PTK) Lck but not transmembrane proteins (CD2, CD4, CD5, CD6, CD8) and PTK ZAP-70 were in part localized in buoyant, lipid-rich, detergent-resistant membrane GPI-microdomains of the COS cells. Endogenous GPI-microdomains of COS cells appear to be, in contrast to those present in leucocytes, essentially devoid of associated PTKs. Our results indicate that GPI-anchor is sufficient to target proteins to these membrane specializations even if expressed ectopically. Moreover, the N-terminal double acylation of the PTK Lck appears to be functional also in COS cells and targets the enzyme to the membrane GPI-microdomains implicated in receptor signalling.

Acylation↗
PubMed1991

Dopamine D1 receptor stimulation of cyclic AMP accumulation in COS-1 cells.

Dopamine is shown to stimulate cAMP accumulation in COS-1 cells via endogenously expressed dopamine D1 receptors. A dissociation of dopamine and beta-adrenoceptor responses is demonstrated by the use of selective antagonists and different desensitization patterns following exposure of the cells to dopamine or the beta-adrenoceptor agonist, isoproterenol. The dopamine response in COS-1 cells exhibits a pharmacological profile similar to that found in dopamine D1 tissues such as rat striatum and fish retina. The presence of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr 32,000) immunoreactivity in COS-1 cells is shown by Western blotting and is consistent with the endogenous expression of a dopamine D1 receptor in these cells. It is concluded that a dopamine D1 receptor is expressed in COS-1 cells and the implications of this are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

[Retroviral vector-mediated in vitro expression of human soluble fas].

Leukemic cells from patients expressed high level FasL cause apoptosis of autologous activated T cells via the Fas/FasL pathway. To investigate the role of soluble Fas (sFas) in reversing this process, a retroviral-mediated expression vector pLXIN-sFas was established. A retroviral-mediated expression system of human sFas was established in vitro and the biological activity of the expression product sFas was observed. To obtain the soluble Fas cDNA, the specific part of the full-length Fas cDNA was deleted by multiple PCR. After pLXIN-sFas packaged by PA317 cells, it was transferred into the target cell COS-7. The quantity of the sFas was (2.2 +/- 0.7) micro g/ml in supernatant of cultured COS-7 cells, and it could greatly inhibit apoptosis of Jurket cells induced by anti-Fas antibody. Our results suggested that the recombinant is able to express the target proteins in vitro and it has the perfect biological activity.

3T3 Cells↗
PubMed2000

Functional properties of recombinant type I and type III inositol 1, 4,5-trisphosphate receptor isoforms expressed in COS-7 cells.

Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are ubiquitous intracellular Ca(2+) release channels whose functional characterization by transfection has proved difficult due to the background contribution of endogenous channels. In order to develop a functional assay to measure recombinant channels, we transiently transfected the rat type I IP(3)R into COS-7 cells. Saponin-permeabilized COS cells transfected with type I IP(3)R showed a 50% increase in inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release at saturating [IP(3)] (10 micrometer) but no enhancement at subsaturating [IP(3)] (300 nm). However, cotransfection of the IP(3)R and human sarco/endoplasmic reticulum ATPase (SERCA)-2b ATPase cDNA resulted in 60 and 110% increases in Ca(2+) release at subsaturating and saturating doses of IP(3), respectively. IP(3) or adenophostin A failed to release (45)Ca(2+) from microsomal vesicles prepared from cells expressing either type I IP(3)R or SERCA cDNAs alone. However, microsomal vesicles prepared from cells doubly transfected with IP(3)R and SERCA cDNAs released 33.0 +/- 0.04% of the A23187-sensitive pool within 30 s of 1 micrometer adenophostin A addition. Similarly, the initial rate of (45)Ca(2+) influx into oxalate-loaded microsomal vesicles was inhibited by IP(3) only when the microsomes were prepared from COS cells doubly transfected with SERCA-2b and IP(3)R DNA. The absence of a functional contribution from endogenous IP(3)Rs has enabled the use of this assay to measure the Ca(2+) sensitivities of IP(3)-mediated (45)Ca(2+) fluxes through recombinant neuronal type I (SII(+)), peripheral type I (SII(-)), and type III IP(3)Rs. All three channels displayed a biphasic dependence upon [Ca(2+)](cyt). Introduction of mutations D2550A and D2550N in the putative pore-forming region of the type I IP(3)R inhibited IP(3)-mediated (45)Ca(2+) fluxes, whereas the conservative substitution D2550E was without effect. This assay therefore provides a useful tool for studying the regulatory properties of individual IP(3)R isoforms as well as for screening pore mutations prior to more detailed electrophysiological analyses.

Adenosine↗
PubMed2004

Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells.

Recently, we and others have shown that luminal K+ recycling via KCNQ1 K+ channels is required for gastric H+ secretion. Inhibition of KCNQ1 by the chromanol 293B strongly diminished H+ secretion. The present study aims at clarifying KCNQ1 subunit composition, subcellular localization, regulation and pharmacology in parietal cells. Using in situ hybridization and immunofluorescence techniques, we identified KCNE2 as the beta subunit of KCNQ1 in the luminal membrane compartment of parietal cells. Expressed in COS cells, hKCNE2/hKCNQ1 channels were activated by acidic pH, PIP2, cAMP and purinergic receptor stimulation. Qualitatively similar results were obtained in mouse parietal cells. Confocal microscopy revealed stimulation-induced translocation of H+,K+-ATPase from tubulovesicles towards the luminal pole of parietal cells, whereas distribution of KCNQ1 K+ channels did not change to the same extent. In COS cells the 293B-related substance IKs124 blocked hKCNE2/hKCNQ1 with an IC50 of 8 nM. Inhibition of hKCNE1- and hKCNE3-containing channels was weaker with IC50 values of 370 and 440 nM, respectively. In conclusion, KCNQ1 coassembles with KCNE2 to form acid-activated luminal K+ channels of parietal cells. KCNQ1/KCNE2 is activated during acid secretion via several pathways but probably not by targeting of the channel to the membrane. IKs124 could serve as a leading compound in the development of subunit-specific KCNE2/KCNQ1 blockers to treat peptic ulcers.

Adenosine Triphosphate↗