Activation of hEAG1 potassium channels by arachidonic acid

Gavrilova-Ruch, O.; Schönherr, Roland; Heinemann, Stefan H.

doi:10.1007/s00424-006-0173-3

Cited by 25 publications

(27 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eag1 channel activity is increased by arachidonic acid in IGR1 melanoma cells (46), and insulin-like growth factor-I increases both channel activity and gene expression of Eag1 in MCF-7 breast cancer cells (47). Here, we show for the first time Eag regulation by cancer risk factors in normal cells.…”

Section: Discussionmentioning

confidence: 53%

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Díaz¹,

Ceja-Ochoa

Restrepo-Angulo³

et al. 2009

Cancer Research

View full text Add to dashboard Cite

Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7). Primary cultures from normal placentas and cervical cancer tissues; tumor cell lines from cervix, choriocarcinoma, keratinocytes, and lung; and normal cell lines from vascular endothelium, keratinocytes, and lung were used. Reverse transcription-PCR (RT-PCR) experiments and Southern blot analysis showed Eag1 expression in all of the cancer cell types, normal trophoblasts, and vascular endothelium, in contrast to normal keratinocytes and lung cells. Estradiol and antiestrogens regulated Eag1 in a cell type-dependent manner. Real-time RT-PCR experiments in HeLa cells showed that Eag1 estrogenic regulation was strongly associated with the expression of estrogen receptor-A. Eag1 protein was detected by monoclonal antibodies in normal placenta and placental blood vessels. Patch-clamp recordings in normal trophoblasts treated with estradiol exhibited potassium currents resembling Eag1 channel activity. Eag1 gene expression in keratinocytes depended either on cellular immortalization or the presence of HPV oncogenes. Eag1 protein was found in keratinocytes transfected with E6/E7 HPV oncogenes. Cell proliferation of E6/E7 keratinocytes was decreased by Eag1 antibodies inhibiting channel activity and by the nonspecific Eag1 inhibitors imipramine and astemizole; the latter also increased apoptosis. Our results propose novel oncogenic mechanisms of estrogen/ antiestrogen use and HPV infection. We also suggest Eag1 as an early indicator of cell proliferation leading to malignancies and a therapeutic target at early stages of cellular hyperproliferation. [Cancer Res 2009;69(8):3300-7]

show abstract

Section: Discussionmentioning

confidence: 53%

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Díaz¹,

Ceja-Ochoa

Restrepo-Angulo³

et al. 2009

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Open-channel blockage by polyunsaturated FFA, apparently by binding of the FFA to an external site in the channel, was also reported for the major voltage-dependent K + channel (Kv1.5) cloned from cardiac cells (Honoré et al, 1994; Guizy et al, 2008). In contrast to this effect, Gavrilova-Ruch et al (2007) reported that AA activated human ether à go-go (hEAG) potassium channels expressed in CHO cells, an effect totally reversed upon washing with BSA. The potentiation effect was directly dependent on the number of cis -double bonds in the FFA, and probably involved a direct mechanism of action, as ETYA also potentiated hEAG currents, presumably acting through the outer membrane leaflet.…”

Section: Ffa Effects On Voltage-gated Ion Channelsmentioning

confidence: 99%

“…The fact that FFA activate hEAG channels whereas they inactivate HERG channels may be due to structural differences in the pore mouth which, in the case of hEAG channels, would prevent the access of AA to the permeation pathway. These channels are normally expressed in neuronal tissue but also in various tumoral tissues, pointing to a possible oncogenic role; the activating effect of AA on EAG channels has therefore been related to an enhanced tumor proliferative rate (Gavrilova-Ruch et al, 2007). …”

Section: Ffa Effects On Voltage-gated Ion Channelsmentioning

confidence: 99%

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Antollini

Barrantes

2016

Front. Physiol.

View full text Add to dashboard Cite

Free fatty acids (FFA) are essential components of the cell, where they play a key role in lipid and carbohydrate metabolism, and most particularly in cell membranes, where they are central actors in shaping the physicochemical properties of the lipid bilayer and the cellular adaptation to the environment. FFA are continuously being produced and degraded, and a feedback regulatory function has been attributed to their turnover. The massive increase observed under some pathological conditions, especially in brain, has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature and in other cases inhibitory. Here we discuss the correlation between the structure of FFA and their ability to modulate protein function, evaluating the influence of saturation/unsaturation, number of double bonds, and cis vs. trans isomerism. We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, contrasting the still conflicting evidence on direct vs. indirect mechanisms of action.

show abstract

“…b, (Béhé et al, 1992; Villarroel, 1993, 1994; Yu, 1995; Doolan et al, 2002; Milberg et al, 2011; Liin et al, 2015, 2016a,b; Moreno et al, 2015). c, (Schledermann et al, 2001; Liu and Wu, 2003; Wang et al, 2004; Guizy et al, 2005; Gavrilova-Ruch et al, 2007). d, (Bregestovski et al, 1989; Kirber et al, 1992; Ling et al, 1992; Ahn et al, 1994; Duerson et al, 1996; Zou et al, 1996; Twitchell et al, 1997; Devor and Frizzell, 1998; Stockand et al, 1998; Denson et al, 1999, 2000, 2005, 2006; Barlow et al, 2000; Wu et al, 2000; Fukao et al, 2001; Lu et al, 2001, 2005; Zhang et al, 2001; Zhang P. et al, 2008; Clarke et al, 2002, 2003; Lauterbach et al, 2002; Li et al, 2002, 2010; Ye et al, 2002; Hamilton et al, 2003; Gauthier et al, 2004, 2014; Zheng et al, 2005, 2008; Yang M. et al, 2005; Sun et al, 2007, 2009; Morin et al, 2007a,b,c; Gebremedhin et al, 2008; Godlewski et al, 2009; Lai et al, 2009; Wang et al, 2011a,b; Enyeart and Enyeart, 2013; Harris et al, 2013; Latorre and Contreras, 2013; Hoshi et al, 2013a,b,c,d; Kacik et al, 2014; Martín et al, 2014; Olszewska et al, 2014; Yan et al, 2014).…”

Section: Effects Of Pufa On Voltage-gated Ion Channelsmentioning

confidence: 99%

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels

2017

View full text Add to dashboard Cite

Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1: The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2: The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3: The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4: The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5: The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels.

show abstract

Activation of hEAG1 potassium channels by arachidonic acid

Cited by 25 publications

References 42 publications

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Estrogens and Human Papilloma Virus Oncogenes Regulate Human Ether-à-go-go-1 Potassium Channel Expression

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels

Contact Info

Product

Resources

About