An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.
An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.
复制标题
针对 H1 的反义寡核苷酸抑制大鼠心室细胞中的经典钠电流，但不抑制 ICa(TTX)。
DOI：
10.1113/jphysiol.2002.035246
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Balke,CWilliam
中科院分区：
文献类型：
--
作者：
Sha,Qun;Robinson,ShawnW;McCulle,StaceyL;Shorofsky,StephenR;Welling,PaulA;Goldman,L;Balke,CWilliam
ICa(TTX)is a sodium current component, functionally distinct from the main body of sodium current, seen in cardiac and other cells. To determine ifICa(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 μm; day 2 of exposure) reduced the classical sodium current by 69.6 % compared to untreated and 60.8 % compared to scrambled sequence (10 μm; 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 onICa(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.
