Alternative splicing of Nav1.5: An electrophysiological comparison of ‘neonatal’ and ‘adult’ isoforms and critical involvement of a lysine residue

Onkal, Rustem; Mattis, Joanna; Fraser, Scott P.; Diss, James K.J.; Shao, Dongmin; Okuse, Kenji; Djamgoz, Mustafa B.A.

doi:10.1002/jcp.21451

Cited by 108 publications

(133 citation statements)

References 52 publications

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“…Exon 6, located in the DI: S3 segment plays an important role in regulating development. The 5' neonatal isoform can be expressed at birth, while the 3' mature isoform is expressed later in development (37). Our study confirmed that the nNav1.5 Na + channel is widely expressed in rat CNS (9,28).…”

Section: Discussionsupporting

confidence: 80%

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Xing

Wang

et al. 2014

Oncology Reports

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Abstract. In the present study, we designed and conducted a series of assays to determine the expression of voltage-gated sodium channel (VGSC) neonatal isoform Nav1.5 (nNav1.5) in human brain astrocytoma and its effect on the proliferation, migration, invasion and apoptosis of astrocytoma U251 cells. The results showed that nNav1.5 mRNA and protein were expressed in both human brain astrocytoma and normal brain tissues, but their expression levels in astrocytoma were significantly higher (P<0.05). In astrocytomas, nNav1.5 mRNA and protein levels were also different (P<0.05) and were correlated with pathological grades. The immunofluorescence confocal microscopy observations demonstrated that nNav1.5 protein was expressed in the nucleus, cytoplasm and membrane of the astrocytoma cells. After transfection, the small interfering RNA (siRNA) targeted to nNav1.5 significantly reduced the expression levels of SCN5A/nNav1.5 mRNA and protein by 57.2% (P<0.05) and 66.6% (P<0.05), respectively. The MTT, wound healing, Matrigel invasion and flow cytometric assays confirmed that following siRNA downregulation of the expression of the SCN5A/nNav1.5 gene, the in vitro proliferation and in vitro invasiveness of the U251 cells were significantly reduced (P<0.05 for both comparisons), and the apoptosis rate was significantly increased (P<0.05). These results revealed that nNav1.5 expression in human brain astrocytoma was upregulated, and its expression was positively correlated with the degree of malignancy. Additionally, reduced nNav1.5 expression significantly suppressed the proliferation and invasiveness of astrocytoma cells, indicating a new target in the molecular diagnosis and therapy of astrocytoma.

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Section: Discussionsupporting

confidence: 80%

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Xing

Wang

et al. 2014

Oncology Reports

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“…Through studies in rat brain, it was possible to conclude that the transcription containing the 5' exon was more common at birth but was quickly replaced by the 3' exon. This splicing pattern has been found in studies with Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6 and Nav1.7 (53 –58). …”

Section: Voltage-gated Na+ Channelssupporting

confidence: 76%

Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

Rhana

Trivelato

Beirão

et al. 2017

Braz J Med Biol Res

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Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.

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“…The first involves simple posttranscriptional changes to the locus, such as RNA editing or alternative splicing (Liu et al, 2004;Onkal et al, 2008). However, our sequence of a nearly complete transcript reveals no such modifications.…”

Section: Discussionmentioning

confidence: 89%

Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism

et al. 2015

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Alternative splicing of Nav1.5: An electrophysiological comparison of ‘neonatal’ and ‘adult’ isoforms and critical involvement of a lysine residue

Cited by 108 publications

References 52 publications

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism

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