A HERG‐like K+ channel in rat F‐11 DRG cell line: pharmacological identification and biophysical characterization.

Faravelli, Laura; Arcangeli, Annarosa; Olivotto, Massimo; Wanke, Enzo

doi:10.1113/jphysiol.1996.sp021661

Cited by 96 publications

(127 citation statements)

References 23 publications

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…During the conditioning step, hERG1 (or hELK2) activates and rapidly inactivates. On repolarisation, the inactivation is removed within milliseconds, revealing a large tail current which decays with a relatively slow kinetics, since the deactivation process is about two orders of magnitude slower than recovery from inactivation (for details on hERG1/hELK2 in cell lines and tumours, see Faravelli et al, 1996;Becchetti et al, 2002). To magnify the K þ currents at practical V m 's, we usually applied our stimuli in the presence of 40 mM external potassium (giving a Nernst potential around À30 mV).…”

Section: Resultsmentioning

confidence: 99%

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

et al. 2005

Self Cite

View full text Add to dashboard Cite

Recent studies have led to considerable advancement in our understanding of the molecular mechanisms that underlie the relentless cell growth and invasiveness of human gliomas. Partial understanding of these mechanisms has (1) improved the classification for gliomas, by identifying prognostic subgroups, and (2) pointed to novel potential therapeutic targets. Some classes of ion channels have turned out to be involved in the pathogenesis and malignancy of gliomas. We studied the expression and properties of K þ channels in primary cultures obtained from surgical specimens: human ether a gò-gò related (hERG)1 voltage-dependent K þ channels, which have been found to be overexpressed in various human cancers, and human ether a gò-gò-like 2 channels, that share many of hERG1's biophysical features. The expression pattern of these two channels was compared to that of the classical inward rectifying K þ channels, IRK, that are widely expressed in astrocytic cells and classically considered a marker of astrocytic differentiation. In our study, hERG1 was found to be specifically overexpressed in high-grade astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas. Our data provide important confirmation for studies proposing the hERG1 channel as a molecular marker of tumour progression and a possible target for novel anticancer therapies.

show abstract

Section: Resultsmentioning

confidence: 99%

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, molecular analysis by RT-PCR revealed that cultured astrocytes express ERG1, but not ERG2-3 genes, suggesting that neuron-specific genes are not constitutively expressed in these glia. The biophysical properties of cloned and native ERG currents are rather complex, and the apparent inward going rectification of these currents closely resembles K IR (Faravelli et al, 1996). Under our experimental conditions, direct investigations of the biophysical properties of astrocytic ERG were impossible, because the syncytial nature of hippocampal (and cultured) astrocytic networks prevents optimal space clamp, and because this current was rarely found in isolation from contaminating currents.…”

Section: Discussionmentioning

confidence: 96%

“…Owing to the large "tail" component of ERG, unambiguous biophysical dissociation of ERG from inward rectification is not always possible (Faravelli et al, 1996), particularly during recordings from glial syncytia where it is possible that multiple cells with different ion channels are contributing to the recorded current (McKhann et al, 1997a,b;D'Ambrosio et al, 1998D'Ambrosio et al, , 1999. ERG and K IR currents can be differentiated, however, by apply- ing methanesulfonanilides, a class of molecules that, at nanomolar concentrations, blocks ERG but not K IR (Kiehn et al, 1996).…”

Section: Erg Expression In Hippocampal or Cultured Astrocytesmentioning

confidence: 99%

“…I Kr is encoded by the human ether-a-go-go-related gene (HERG) (Sanguinetti et al, 1995;Trudeau et al, 1995), first identified from a hippocampal cDNA library (Warmke and Ganetzky, 1994). A similar current, originally attributed to the inward rectifier family but pharmacologically related to HERG (Faravelli et al, 1996), strongly resembles the glial inward rectifier (Ransom and Sontheimer, 1995;Ransom et al, 1996). Furthermore, the characteristic time and voltage dependence of ERG produces large inward and only small outward whole-cell currents (Warmke and Ganetzky, 1994), resulting in apparent inward-going rectification such as seen in CNS astrocytes.…”

Section: Abstract: Spatial Buffering; Glia-neuronal Interactions; Epmentioning

confidence: 99%

“…Furthermore, the amplitude of the currents not affected by ERG blockers varied greatly across cells, suggesting that in addition to ERG, variable levels of K IR expression are present in these glia (Guatteo et al, 1996;Bordey and Sontheimer, 1997;D'Ambrosio et al, 1998D'Ambrosio et al, , 1999. K IR currents are blocked by low concentrations of Cs ϩ (Ransom and Sontheimer, 1995), whereas concentrations Ͼ2 mM are required to affect ERG (Faravelli et al, 1996). We compared the sensitivity of hippocampal astrocyte currents to concentrations of Cs ϩ specific for K IR versus treatment with dofetilide at concentrations specific for ERG (Fig.…”

Section: Coexistence Of K Ir and Erg Currentsmentioning

confidence: 99%

See 2 more Smart Citations

Do Glia Have Heart? Expression and Functional Role forEther-A-Go-GoCurrents in Hippocampal Astrocytes

et al. 2000

View full text Add to dashboard Cite

Potassium homeostasis plays an important role in the control of neuronal excitability, and diminished buffering of extracellular K results in neuronal Hyperexcitability and abnormal synchronization. Astrocytes are the cellular elements primarily involved in this process. Potassium uptake into astrocytes occurs, at least in part, through voltage-dependent channels, but the exact mechanisms involved are not fully understood. Although most glial recordings reveal expression of inward rectifier currents (K IR ), it is not clear how spatial buffering consisting of accumulation and release of potassium may be mediated by exclusively inward potassium fluxes. We hypothesized that a combination of inward and outward rectifiers cooperate in the process of spatial buffering. Given the pharmacological properties of potassium homeostasis (sensitivity to Cs ϩ ), members of the ether-a-go-go (ERG) channel family widely expressed in the nervous system could underlie part of the process. We used electrophysiological recordings and pharmacological manipulations to demonstrate the expression of ERG-type currents in cultured and in situ hippocampal astrocytes. Specific ERG blockers (dofetilide and E 4031) inhibited hyperpolarizationand depolarization-activated glial currents, and ERG blockade impaired clearance of extracellular potassium with little direct effect on hippocampal neuron excitability. Immunocytochemical analysis revealed ERG protein mostly confined to astrocytes; ERG immunoreactivity was absent in presynaptic and postsynaptic elements, but pronounced in glia surrounding the synaptic cleft. Oligodendroglia did not reveal ERG immunoreactivity. Intense immunoreactivity was also found in perivascular astrocytic end feet at the blood-brain barrier. cDNA amplification showed that cortical astrocytes selectively express HERG1, but not HERG2-3 genes. This study provides insight into a possible physiological role of hippocampal ERG channels and links activation of ERG to control of potassium homeostasis.

show abstract

Modulation of HERG current andherg gene expression during retinoic acid treatment of human neuroblastoma cells: Potentiating effects of BDNF

et al. 1999

View full text Add to dashboard Cite

The modulation of herg gene and HERG currents (IHERG) was studied in SH‐SY5Y neuroblastoma (NB) cells treated with all‐trans‐retinoic acid (RA) in the absence or presence of the neurotrophin brain‐derived neurotrophic factor (BDNF). Both treatments produced a strong increase in the percentage of cells differentiated along the neuronal pathway, with an orientation to a cholinergic phenotype, while a minority of cells displayed a glial phenotype particularly evident after long‐term exposure to the inducers. Differentiation of NB cells was accompanied by an increase in herg gene transcription, which attained its maximum after 6 days of treatment with RA and was not further increased by BDNF. This effect evidently reflected on HERG currents: In fact, RA produced an increase in HERG current density which was strongly potentiated by BDNF. Moreover, RA treatment affected the biophysical properties of IHERG, inducing an increase in the deactivation time constant and a left shift of the activation curve. These effects were not substantially affected by BDNF. This modulation of IHERG influenced the value of the resting potential (VREST), which resulted significantly hyperpolarized in (RA with or without BDNF)‐treated cells. Interestingly, these effects were absent in the glial population, which prevailed in cultures after long‐term exposure to the inducers. On the whole, we demonstrate that besides expressing IRK currents, NB cells display another strategy to hyperpolarize their VREST, based on the appropriate modulation of HERG currents. Different from what happens in normal neuroblast development, the latter are never lost by cancer cells despite the progression of these cells along the neuronal differentiative pathway, raising intriguing questions about the role of HERG currents in tumour behavior. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 214–225, 1999

show abstract

A HERG‐like K+ channel in rat F‐11 DRG cell line: pharmacological identification and biophysical characterization.

Abstract: 1. The relationships between the K+ inward rectifier current present in neuroblastoma cells (IIR)

Cited by 96 publications

References 23 publications

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

Do Glia Have Heart? Expression and Functional Role forEther-A-Go-GoCurrents in Hippocampal Astrocytes

Modulation of HERG current andherg gene expression during retinoic acid treatment of human neuroblastoma cells: Potentiating effects of BDNF

Contact Info

Product

Resources

About