右美托咪定对心室肌细胞L型钙通道电流的影响

Effects of dexmedetomidine on L-type calcium current in rat ventricular myocytes

目的观察右美托咪定(DEX)对大鼠心室肌细胞L型钙离子通道电流(ICa-L)的影响,探讨其对心脏电活动影响的机制。方法取SD大鼠,用酶解法分离获得单个心室肌细胞,采用全细胞膜片钳技术记录ICa-L,观察不同浓度的DEX(0.6,1.8,5.4,10,200 ng/ml)以及1μmol/L育亨宾(α2肾上腺素受体拮抗剂)单独使用及与10 ng/ml DEX联合使用对ICa-L的影响。结果 0.6,1.8,5.4,10,200 ng/ml的DEX对峰电流的抑制率分别为8.8%±2.4%、14.6%±3.6%、21.4%±8.4%、25.2%±6.4%和32.1%±6.6%,使I-V曲线上移。小剂量(0.6,1.8,5.4 ng/ml)的DEX对ICa-L激活曲线无明显影响(n=6,P>0.05);大剂量(10和200 ng/ml)的DEX可使ICa-L激活曲线右移。0.6,1.8,5.4,10,200 ng/ml的DEX可使ICa-L失活后恢复时间延长。10 ng/ml的DEX可使ICa-L的峰值抑制约25.2%±6.4%,再向电极外液中加入育亨宾后ICa-L平均增加约15%(n=6,P<0.05)。1μmol/L育亨宾灌流前后ICa-L的峰值无差异(n=6,P>0.05)。结论 DEX对心室肌细胞ICa-L具有浓度依赖性地抑制作用,可能是通过细胞膜上的α2肾上腺素受体介导的。

Objective To investigate the effects of dexmedetomidine（DEX） on L-type calcium current（ ICa-L ）in isolated rat ventricular myocytes. Methods The cardiac ventricular myocytes of rats were isolated enzymatically and the whole cell patch clamp technique was used to investigated the effects of DEX （0.6, 1.8, 5.4, 10,200 ng/ml） on ICa-L in isola- ted rat ventricular myocytes. Besides, the effects of 1 μmol/L yohimbine, an α2-antagonist, were given alone or in combi- nation with 10 ng/ml DEX. Results DEX inhibited the amplitude of ICa-L in a concentration dependent manner. The suppression ratios were 8.8% ±2.4% ,14.6%±3.6% ,21.4% ±8.4% ,25.2% ±6.4% and 32.1% ±6.6% at 0.6, 1.8, 5.4, 10 and 200 ng/ml （ n = 6, P 〈 0.05 ）. The current-voltage curve was shifted upwards. The steady activated curves were shifted to the right and the V1/2 activation of the ICa-L were increased by DEX at high concentration （ 10 and 200 ng/ml）. DEX did not affect the ICa-L steady-state inactivation curve, but shifted down the recovery curve. Yohimbine did not have influence on ICa-L. However, inhibition of ICa-L by DEX at the concentration of 10 ng/ml was partially reversed by yohimbine. Conclusion DEX can attenuate ICa-L, which may contribute to its negative effects on myoeardia contrac- tility and cardiac electrophysiology. The inhibitory effect of DEX on ICa-L in isolated ventricular myoeytes is partially associ- ated with α2 -adrenergic receptors.