RGD Reference Report - An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells. - Rat Genome Database

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An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.

Authors: Sha, Q  Robinson, SW  McCulle, SL  Shorofsky, SR  Welling, PA  Goldman, L  Balke, CW 
Citation: Sha Q, etal., J Physiol. 2003 Mar 1;547(Pt 2):435-40. Epub 2003 Jan 24.
RGD ID: 6484230
Pubmed: (View Article at PubMed) PMID:12562928
DOI: Full-text: DOI:10.1113/jphysiol.2002.035246

ICa(TTX) is a sodium current component, functionally distinct from the main body of sodium current, seen in cardiac and other cells. To determine if ICa(TTX) channels are a separate isoform from the classical cardiac sodium channels, we exposed rat ventricular cells in primary culture to an antisense oligonucleotide (AON) directed against rH1 (rNav1.5): 5'-CTCCTCATACCCTCT-3'. The homologous human sequence has been identified (and confirmed by us on HEK 293 cells) as effective against hH1 expressed heterologously. Scrambled sequence (5'-CCCCCCTTATCTACT-3') controls were also included. The AON (10 microM; day 2 of exposure) reduced the classical sodium current by 69.6 % compared to untreated and 60.8 % compared to scrambled sequence (10 microM; day 2 of exposure) controls (mean +/- S.E.M. maximum peak inward current density of -8.23 +/- 0.60 pA pF-1, 18 cells, for untreated; -6.37 +/- 0.79 pA pF-1, 16 cells, for scrambled sequence; and -2.50 +/- 0.31 pA pF-1, 18 cells, for AON-treated cells). The two control groups are not significantly different from each other, but are both significantly different from the AON-treated group (P < 0.001). The inhibition was specific for sodium channels, with no significant AON effect on the L-type calcium current. This confirms that H1 generates the classical cardiac sodium current. This same AON at the same concentration and time of exposure had no significant effect on ICa(TTX) (mean of -4.72 +/- 0.55, 15 cells; -5.47 +/- 0.53, 13 cells; and -5.04 +/- 0.63 pA pF-1, 15 cells, for untreated controls, scrambled controls and AON treated, respectively). Hence, ICa(TTX), which is functionally distinct from the classical cardiac sodium current, is encoded by a distinct gene.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Scn5a  (sodium voltage-gated channel alpha subunit 5)


Additional Information