Toxin and kinetic profile of rat brain type III sodium channels expressed in Xenopus oocytes

Joho, Rolf H.; Moorman, J. Randall; VanDongen, Antonius M.J.; Kirsch, Glenn E.; Silberberg, Hanna; Schuster, Gabriele; Brown, Arthur M.

doi:10.1016/0169-328x(90)90087-t

Cited by 91 publications

(49 citation statements)

References 32 publications

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“…By contrast, when the cell membrane was depolarised to 22361 mV by using veratridine, I Na,P was enhanced. Consistent with these findings, the intracellular Na Na v channels typically comprise one pore-forming a subunit and one or two auxiliary b subunits that modulate channel gating and cell surface expression (Catterall, 2000;Joho et al, 1990). b subunits, particularly b1, also function as cell adhesion molecules (CAMs) (Brackenbury and Isom, 2008;Chioni et al, 2009;Isom, 2001;Isom, 2002;Patino and Isom, 2010).…”

Section: Na V Promotes H460 Cell Invasionmentioning

confidence: 90%

Functional expression of the voltage-gated sodium channel, Nav1.7, underlies epidermal growth factor-mediated invasion in human [R1.S1] non-small cell lung cancer cells

Campbell¹,

Main²,

FitzGerald³

2013

Journal of Cell Science

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SummaryVarious ion channels are expressed in human cancers where they are intimately involved in proliferation, angiogenesis, invasion and metastasis. Expression of functional voltage-gated Na + channels (Na v ) is implicated in the metastatic potential of breast, prostate, lung and colon cancer cells. However, the cellular mechanisms that regulate Na v expression in cancer remain largely unknown. Growth factors are attractive candidates; they not only play crucial roles in cancer progression but are also key regulators of ion channel expression and activity in non-cancerous cells. Here, we examine the role of epidermal growth factor receptor (EGFR) signalling and Na v in non-small cell lung carcinoma (NSCLC) cell lines. We show unequivocally, that functional expression of the a subunit Na v 1.7 promotes invasion in H460 NSCLC cells. Inhibition of Na v 1.7 activity (using tetrodotoxin) or expression (by using small interfering RNA), reduces H460 cell invasion by up to 50%. Crucially, non-invasive wild type A549 cells lack functional Na v , whereas exogenous overexpression of the Na v 1.7 a subunit is sufficient to promote TTX-sensitive invasion of these cells. EGF/EGFR signalling enhances proliferation, migration and invasion of H460 cells but we find that, specifically, EGFR-mediated upregulation of Na v 1.7 is necessary for invasive behaviour in these cells. Examination of Na v 1.7 expression at mRNA, protein and functional levels further reveals that EGF/ EGFR signalling via the ERK1/2 pathway controls transcriptional regulation of channel expression to promote cellular invasion. Immunohistochemistry of patient biopsies confirms the clinical relevance of Na v 1.7 expression in NSCLC. Thus, Na v 1.7 has significant potential as a new target for therapeutic intervention and/or as a diagnostic or prognostic marker in NSCLC.

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Section: Na V Promotes H460 Cell Invasionmentioning

confidence: 90%

Functional expression of the voltage-gated sodium channel, Nav1.7, underlies epidermal growth factor-mediated invasion in human [R1.S1] non-small cell lung cancer cells

Campbell¹,

Main²,

FitzGerald³

2013

Journal of Cell Science

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“…3D). This indicates that PN1 is a TTXsensitive sodium channel, with TTX sensitivity similar to that of the rBIIA (32), rSkM1 (33), rBIII (34,35), and hNE (8) channels but with much higher sensitivity than the cardiac (36,37) and PN3/SNS (4, 5) sodium channels.…”

Section: Fig 4 Inward Currents Induced Inmentioning

confidence: 93%

A Novel Tetrodotoxin-sensitive, Voltage-gated Sodium Channel Expressed in Rat and Human Dorsal Root Ganglia

Sangameswaran¹,

Fish²,

Koch³

et al. 1997

Journal of Biological Chemistry

254

168

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Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal root ganglia (DRG), cellular expression, and functional analysis of a novel tetrodotoxin-sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many different tissues. Within the rat DRG, both the mRNA and PN1-like immunoreactivity are present in small and large neurons. The abundance of sodium channel mRNAs in rat DRG is rBI > PN1 PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction analysis. Data from reverse transcription-polymerase chain reaction and sequence analyses of human DRG and other human tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel. In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium currents and is inhibited by tetrodotoxin with an IC 50 of 4.3 ؎ 0.92 nM. Unlike rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression of the ␤-subunits.

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“…It negatively shifts the voltage dependence of activation of the rat neuronal Na v 1.2 channel but only after the channel is ''primed'' with a preceding depolarizing prepulse in the presence of toxin (21). ␤ scorpion toxins have similar effects on Na v 1.3 (22). If it were also active on Na v 1.1 and Na v 1.6, CssIV could serve as a specific tool to reveal a low level of sodium current conducted by Na v 1.1, Na v 1.3, and Na v 1.6 in myocytes.…”

Section: Detection Of Ina Conducted By Brain-type Sodium Channels Aftermentioning

confidence: 98%

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

Maier

Westenbroek

Schenkman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

266

250

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Voltage-gated sodium channels composed of pore-forming ␣ and auxiliary ␤ subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac poreforming ␣ subunit isoform Nav1.5 is preferentially localized in intercalated disks, whereas the brain ␣ subunit isoforms Nav1.1, Nav1.3, and Nav1.6 are localized in the transverse tubules. Sodium currents due to the highly tetrodotoxin (TTX)-sensitive brain isoforms in the transverse tubules are small and are detectable only after activation with ␤ scorpion toxin. Nevertheless, they play an important role in coupling depolarization of the cell surface membrane to contraction, because low TTX concentrations reduce left ventricular function. Our results suggest that the principal cardiac isoform in the intercalated disks is primarily responsible for action potential conduction between cells and reveal an unexpected role for brain sodium channel isoforms in the transverse tubules in coupling electrical excitation to contraction in cardiac muscle.

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Toxin and kinetic profile of rat brain type III sodium channels expressed in Xenopus oocytes

Cited by 91 publications

References 32 publications

Functional expression of the voltage-gated sodium channel, Nav1.7, underlies epidermal growth factor-mediated invasion in human [R1.S1] non-small cell lung cancer cells

Functional expression of the voltage-gated sodium channel, Nav1.7, underlies epidermal growth factor-mediated invasion in human [R1.S1] non-small cell lung cancer cells

A Novel Tetrodotoxin-sensitive, Voltage-gated Sodium Channel Expressed in Rat and Human Dorsal Root Ganglia

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

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