肾上腺髓质素对脓毒性休克大鼠心肌细胞外向钾电流的影响

目的 研究肾上腺髓质素(ADM)对脓毒性休克大鼠心肌细胞外向钾电流的影响.方法 成年大鼠腹腔注射脂多糖(LPS,10 mg/kg)4 h后,分离心室肌细胞.用全细胞膜片钳的方法 记录瞬时外向钾电流(I_(to)),稳态钾电流(I_(ss))和ATP敏感钾电流(I_(K,ATP)).结果 LPS处理对I_(to)和I_(ss)无影响.休克心肌细胞I_(K,ATP)密度(2.66 ± 0.56)pA/pF(n=12)]较正常心肌细胞值(0.27 ± 0.08)pA/pF(n=14)]明显增加(P＜0.01).ADM受体拮抗剂ADM-(22-52)可使增加的I_(K,ATP)得到明显的恢复(0.69 ± 0.21)pA/pF(n=11),P＜0.01 vs LPS 组].而ADM-(22-52)与100 μmol/L氨基胍联合处理几乎可完全取消I_(K,ATP)的增加.结论 脓毒性休克大鼠心肌细胞I_(K,ATP)被激活.ADM 与NO共同参与了脓毒性休克大鼠心肌细胞I_(K,ATP)的激活.

Effects of Adrenomedullin on Outward Potassium Current in Myocytes from Septic Shock Rats

Objective To study the outward potassium current in myocytes from septic shock rats and the effects of adrenomedullin(ADM).Methods Ventricular myocytes were isolated from adult rats 4 h after an intraperitoneal injection of lipopolysaccharide(LPS,10 mg/kg).Transient outward K~+ current(I_(to)),steady-state K+ current(I_(ss))and ATP sensitive potassium current(I_(K,ATP))were recorded using whole cell patch-clamp methods.Results LPS treatment had no effect on Ito and Iss.The I_(K,ATP) density in septic shock group(2.66±0.56) pA/pF,n=12]was significantly higher than that in control group(0.27±0.08) pA/pF,n=14,P＜0.01].The ADM antagonist ADM-(22-52)significantly reversed the increased I_(K,ATP)(0.69±0.21) pA/pF,n=11,P＜0.01 vs LPS group]in shock myocytes.I_(K,ATP) density was lower in LPS plus aminoguanidine myocytes(0.77±0.18) pA/pF,n=10,P＜0.01 vs LPS group]than that in LPS myocytes.ADM-(22-52)and 100 μmol/L aminoguanidine could completely abolish the increase in I_(K,ATP).Conclusion I_(K,ATP) was activated in myocytes from septic shock rats.Adrenomedullin along with NO precipitated activation of the I_(K,ATP) in rat ventricular myocytes during septic shock.