Zhong Guang-Zhen, Li Yan-Bing, Liu Xiu-Lan, Guo Lei-Sheng, Chen Mu-lei, Yang Xin-Chun
Department of Cardiology, Beijing Chaoyang Hospital, and Cardiovascular Institute, Capital Medical University, Beijing, PR China.
Cardiology. 2010;115(2):120-6. doi: 10.1159/000260073. Epub 2009 Nov 19.
Hydrogen sulfide (H(2)S), an endogenous gaseous transmitter, was found to protect the heart from various forms of injury, but the underlying mechanism is not known. H(2)S can open the K(ATP) channel on vascular smooth muscle cells, and the objective of this study was to determine whether H(2)S can open the K(ATP) channel on myocardiocytes.
The whole-cell patch-clamp technique was used to record I(K,ATP) and action potentials of atrial and ventricular myocytes isolated from the hearts of male Wistar rats. Sodium hydrogen sulfide (NaHS) was used as a donor of H(2)S to observe the effect of exogenous H(2)S on I(K,ATP). DL-propargylglycine (PPG), an inhibitor of the synthesis of H(2)S, was used at a concentration of 200 microM to observe the effect of endogenous H(2)S on I(K,ATP).
NaHS at concentrations (in microM) of 9.375, 18.75, 37.5, 75 and 150 increased I(K,ATP) by 12.8% (p > 0.05), 28.4% (p < 0.05), 38.8% (p < 0.01), 51.2% (p < 0.01) and 58.6% (p< 0.01) on ventricular myocytes, respectively, and by 6.8% (p > 0.05), 10.4% (p > 0.05), 18.9% (p < 0.01), 24.8% (p < 0.01) and 37.2% (p < 0.01) on atrial myocytes, respectively. The H(2)S-induced decrease in the duration of action potentials (APD(90)) of ventricular myocytes was concentration-dependent, although only NaHS at a concentration of 150 microM decreased the APD(90) significantly (15%, p < 0.05). The H(2)S-induced decrease in APD(90) on atrial myocytes was concentration dependent, but the statistical difference was not significant. Inhibition of I(K,ATP) by PPG was time dependent and the level of inhibition was: ventricular myocytes, 7% (p > 0.05), 10% (p < 0.05), 15.3% (p < 0.01), 24.0% (p < 0.01) and 28.9% (p < 0.01); atrial myocytes, 15.8% (p > 0.05), 21.3% (p > 0.05), 26.5% (p < 0.01), 34.0% (p < 0.01) and 43.2% (p < 0.01) measured at 5, 10, 15, 20 and 25 min, respectively. The increase in the APD(90), by PPG was time dependent for ventricular myocytes [increased by 12.8% (p < 0.05) at 25 min]. The same was true for atrial myocytes, although only the value at 25 min was significant (15%, p < 0.05).
H(2)S decreased the APD(90),and both the endogenous and exogenous H(2)S-induced increase in I(K,ATP) on both atrial and ventricular myocytes was concentration dependent. These results may help to explain, at least in part, how H(2)S protects heart cells from various forms of injury.
硫化氢（H₂S）作为一种内源性气体递质，已被发现可保护心脏免受多种形式的损伤，但其潜在机制尚不清楚。H₂S可开启血管平滑肌细胞上的ATP敏感性钾通道（KATP通道），本研究的目的是确定H₂S是否能开启心肌细胞上的KATP通道。
采用全细胞膜片钳技术记录从雄性Wistar大鼠心脏分离的心房和心室肌细胞的KATP电流（IK,ATP）及动作电位。使用硫氢化钠（NaHS）作为H₂S的供体，观察外源性H₂S对IK,ATP的影响。使用硫化氢合成抑制剂DL-炔丙基甘氨酸（PPG），浓度为200μM，观察内源性H₂S对IK,ATP的影响。
浓度为9.375、18.75、37.5、75和150μM的NaHS分别使心室肌细胞的IK,ATP增加12.8%（p>0.05）、28.4%（p<0.05）、38.8%（p<0.01）、51.2%（p<0.01）和58.6%（p<0.01），使心房肌细胞的IK,ATP分别增加6.8%（p>0.05）、10.4%（p>0.05）、18.9%（p<0.01）、24.8%（p<0.01）和37.2%（p<0.01）。H₂S诱导的心室肌细胞动作电位时程（APD90）缩短呈浓度依赖性，尽管只有浓度为150μM的NaHS能显著缩短APD90（15%，p<0.05）。H₂S诱导的心房肌细胞APD90缩短也呈浓度依赖性，但统计学差异不显著。PPG对IK,ATP的抑制作用呈时间依赖性，抑制水平为：心室肌细胞在5、10、15、20和25分钟时分别为7%（p>0.05）、10%（p<0.05）、15.3%（p<0.01）、24.0%（p<0.01）和28.9%（p<0.01）；心房肌细胞在相应时间分别为15.8%（p>0.05）、21.3%（p>0.05）、26.5%（p<0.01）、34.0%（p<0.01）和43.2%（p<0.01）。PPG使心室肌细胞的APD90增加也呈时间依赖性（25分钟时增加12.8%，p<0.05）。心房肌细胞也是如此，尽管只有25分钟时的值具有统计学意义（15%，p<0.05）。
H₂S可缩短APD90，内源性和外源性H₂S诱导的心房和心室肌细胞IK,ATP增加均呈浓度依赖性。这些结果可能至少部分有助于解释H₂S如何保护心脏细胞免受多种形式的损伤。
