β_3肾上腺素能受体激动对慢性心力衰竭大鼠心房肌细胞瞬时外向钾电流的影响

Effect of β_3-adrenoreceptor stimulation on atrial transient outward potassium current in rats with chronic heart failure

目的探讨选择性β_3肾上腺素能受体(β_3-adrenoreceptor,β_3-AR)激动剂BRL-37344对慢性心力衰竭(chronic heart failure,CHF)大鼠左心房肌细胞瞬时外向钾电流(I_(to))的影响。方法 26只雄性Wistar大鼠随机分为假手术组(Sham组,n=6)和CHF组(n=20),CHF大鼠模型的建立采用主动脉缩窄法。CHF组大鼠再被分为CHF对照组和BRL组(经尾静脉注射BRL-37344 0.4 nmol/kg,每周2次,共4周)。采用酶解法分离获得大鼠左心房肌细胞。左心房肌细胞I_(to)的测定采用全细胞膜片钳技术(以电流密度pA/pF表示)。结果当指令电压为+60 mV时,Sham组,CHF组、BRL组大鼠左心房肌细胞I_(to)电流密度达最大值,分别为(20.85±3.44)pA/pF、(11.54±1.21)pA/pF、(6.29±1.50)pA/pF。当指令电压从+60 mV至+30 mV时,BRL组和CHF对照组I_(to)电流密度均显著低于Sham组,差异有统计学意义(P<0.01);BRL组显著低于CHF对照组,差异有统计学意义(P<0.05或0.01)。当指令电压从+20 mV至0 mV时,BRL组和CHF对照组I_(to)电流密度均显著低于Sham组,差异有统计学意义(P<0.01);但BRL组与CHF对照组之间比较,差异无统计学意义(P>0.05)。结论β_3-AR选择性激动剂BRL-37344显著抑制了CHF大鼠心房肌细胞I_(to)电流密度。

Objectives To investigate the effect of selective β3-adrenoreceptor （β3-AR） agonist BRL-37344 on transient outward potassium current （Ito） in the left atrial myoeytes of rats with chronic heart failure （CHF）. Methods The CHF rat model was established by aortic constriction. Twenty-six male Wistar rats were divided into sham-operated group （sham group, n=6） and CHF group （n=20）, which were further divided into CHF control and BRL groups. The rats in BRL group received BRL-37344 via tail vein injection, 0.4 nmol/kg, twice a week for four weeks. The left atrial myoeytes were enzymatically dissociated by Langendorff perfusion. I,o was measured by whole-cell patch-clamp technique, expressed as current density pA/pF. Results When command potential was at ＋60 mV, Ito densities were （20.85±3.44） pA/pF in sham group, （11.54±1.21） pA/pF in CHF control group and （6.29±1.50） pA/pF in BRL group, achieving the maximum value. When command potential was between ±60 mV and ±30 mV, Ito densities in CHF control group and BRL group were significantly lower than that in sham group （P〈0.01）, and Ito density in BRL group was significantly lower than that in CHF control group （P〈0.05 or ≤ 0.01 ）. When command potential was between ＋20 mV and 0 mV, Ito densities in CHF control group and BRL group were significantly lower than that in sham group （P〈 0.01 ）; but there was no difference in I,o density between BRL group and CHF control group （P〉0.05）. Conclusions Selective β3-AR agonist BRL-37344 obviously inhibits I,o in the left atrial myocytes of CHF rats.