The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+.

Stanfield, Peter; Davies, Noel W.; Shelton, Philip A.; Khan, Iftikhar Ahmad; Brammar, William J.; Standen, N B; Conley, Edward C.

doi:10.1113/jphysiol.1994.sp020044

Cited by 94 publications

(96 citation statements)

References 16 publications

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“…3B). This is consistent with the expression of the Kir2,1 gene to produce a homotetrameric Kir2.1 channel [7,15]. The current-voltage relation for this cell is illustrated in Fig.…”

Section: Functional Expression Of Kir21supporting

confidence: 60%

“…The inward rectifier mIRK1 (Kir2.1) coding sequence [11] was isolated on an EcoRI-XhoI fragment from a PCR derived clone [7] and cloned between the same sites of pCLAPE6 (Fig. 2).…”

Section: Production Of the Lap Expression Vector Pclape6 Andmentioning

confidence: 99%

“…Following stable transfection into mouse erythroleukaemia (MEL) cells and subsequent induction to differentiation, high levels of heterologous protein can be produced. The system has been routinely used in our laboratory for the stable and functional expression of K + channel cDNAs and genes [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

Shelton

Dart

1996

FEBS Letters

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Locus control regions (LCRs) are cis-acting elements that confer position-independent and copy-nnmber-dependent expression upon associated genes in transgenic mice. Here we show the second example of the use of an LCR (the rat LAP LCR) in a stable expression vector system, used here in conjunction with the rat liver (NRLM) cell line. Non-transfected NRLM cells are electrically silent and highly suitable for patch clump electrophysiology. We report reliable constitutive expression from two different K + channel cDNAs; the voltage-gated rat clone Kv3.4 and the inward rectifier mouse clone Kir2.1. We further show that constitutive expression levels are stable for at least 8 weeks from initial recording.

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“…3B). This is consistent with the expression of the Kir2,1 gene to produce a homotetrameric Kir2.1 channel [7,15]. The current-voltage relation for this cell is illustrated in Fig.…”

Section: Functional Expression Of Kir21supporting

confidence: 60%

“…The inward rectifier mIRK1 (Kir2.1) coding sequence [11] was isolated on an EcoRI-XhoI fragment from a PCR derived clone [7] and cloned between the same sites of pCLAPE6 (Fig. 2).…”

Section: Production Of the Lap Expression Vector Pclape6 Andmentioning

confidence: 99%

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The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

Shelton

Dart

1996

FEBS Letters

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“…1) are crucial for the inward rectification of Kir channels. One is in the second transmembrane segment (21,23,24), and the other is in the cytoplasmic C-terminal domain (25,26). Channels such as Kir2.1-Kir2.4, with two negatively charged amino acids in these positions, confer strong rectification (24,58), whereas those with neutral or positively charged amino acids produce weak rectification, e.g.…”

Section: Kir41 In the Inner Earmentioning

confidence: 99%

“…The inward rectification of Kir channels is caused by both blockage of the outward current by cytoplasmic Mg 2ϩ and by intrinsic polyamines (21)(22)(23)(24)(25)(26). We surmised that DFMO-induced ototoxicity is mediated through inhibition of polyamine synthesis, consequently altering inward rectification of inner ear-specific Kir4.1.…”

Section: L-␣-difluoromethylornithine (Dfmo)mentioning

confidence: 99%

Functional Consequences of Polyamine Synthesis Inhibition by l-α-Difluoromethylornithine (DFMO)

Nie

Feng

Diaz

et al. 2005

Journal of Biological Chemistry

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L-␣-Difluoromethylornithine (DFMO) is a chemopreventive agent for colon cancer in clinical trials. Yet, the drug produces an across-frequency elevation of the hearing threshold, suggesting that DFMO may affect a common trait along the cochlear spiral. The mechanism for the ototoxic effects of DFMO remains uncertain. The cochlear duct is exclusively endowed with endocochlear potential (EP). EP is a requisite for normal sound transduction, as it provides the electromotive force that determines the magnitude of the receptor potential of hair cells. EP is generated by the high throughput of K ؉ across cells of the stria vascularis, conferred partly by the activity of Kir4.1 channels. Here, we show that the ototoxicity of DFMO may be mediated by alteration of the inward rectification of Kir4.1 channels, resulting in a marked reduction in EP. These findings are surprising given that the present model for EP generation asserts that Kir4.1 confers the outflow of K ؉ in the stria vascularis. We have proposed an alternative model. These findings should also enable the rational design of new pharmaceuticals devoid of the untoward effect of DFMO.

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Myocardial K⁺Channels: Primary Determinants of Action Potential Repolarization

Niwa¹,

Nerbonne²

2009

Novel Therapeutic Targets for Antiarrhythmic Drugs

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The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+.

Cited by 94 publications

References 16 publications

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

Functional Consequences of Polyamine Synthesis Inhibition by l-α-Difluoromethylornithine (DFMO)

Myocardial K⁺Channels: Primary Determinants of Action Potential Repolarization

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The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+.

Cited by 94 publications

References 16 publications

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K+ channel cDNAs in a rat liver cell line

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K+ channel cDNAs in a rat liver cell line

Functional Consequences of Polyamine Synthesis Inhibition by l-α-Difluoromethylornithine (DFMO)

Myocardial K+Channels: Primary Determinants of Action Potential Repolarization

Contact Info

Product

Resources

About

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

The use of the rat LAP LCR and promoter for the high‐level constitutive expression of K⁺ channel cDNAs in a rat liver cell line

Myocardial K⁺Channels: Primary Determinants of Action Potential Repolarization