硫化氢对哇巴因诱发的豚鼠乳头肌迟后去极化及触发活动的影响

目的 探讨硫化氢(H2S)对哇巴因诱发的豚鼠乳头肌迟后去极化(DAD)及触发活动的影响及其可能的机制.方法 应用细胞内玻璃微电极技术记录含哇巴因的高钙K-H液诱发的DAD和触发活动.随机数字表法将豚鼠分为哇巴因组、哇巴因+NaHS组、哇巴因+NaHS+格列苯脲组、哇巴因+ NaHS+ Bay K8644组和哇巴因+NaHS+左旋硝基精氨酸甲酯(L-NAME)组5组,各6只.观察硫氢化钠( NaHS)预处理对DAD和触发活动的影响,格列苯脲(20 μmol/L),Bay K8644(0.25 μmol/L),L-NAME(1 mmol/L)预处理对H2S作用的影响.结果 NaHS( 100、200 μmol/L)预处理DAD的潜伏期分别为(19.9±1.6) min、(23.7±1.3) min,均长于哇巴因组(12.0±1.0) min,P＜0.05或＜0.01];幅值分别为(6.47±0.33) mV、(5.65±0.26) mV,均低于哇巴因组(11.47±0.74) mV,均P＜0.01];时程分别为(173±10) ms、( 134±7) ms,均短于哇巴因组(205±11) ms,P＜0.05];在每组6个标本中,有触发活动的发生的标本数分别为4、2、1个,而哇巴因组6个标本中,5个出现触发活动(P ＜0.05或P＜0.01);预先应用格列苯脲(20 μmol/L)部分阻断NaHS(100 μmol/L)的作用;Bay K8644(0.25μmol/L)可完全阻断NaHS的作用;L-NAME(1mmol/L)对NaHS的作用无影响.结论 H2S具有抑制乳头肌DAD及触发活动的作用,其机制可能与兴奋三磷酸腺苷(ATP)敏感的钾通道促进K+外流,抑制Ca2+内流有关.

Effects of hydrogen sulfide on ouabain-induced delayed after-depolarization and triggered activity in guinea pig papillary muscles

Objective To explore the effects of hydrogen sulfide (H2S) on delayed afterdepolarization (DAD) and triggered activity induced by ouabain in male guinea pig papillary muscles and to elucidate the underlying mechanisms.Methods An intracellular microelectrode was used to record the patterns of DAD and triggered activity by K-H solution containing ouabain and a high concentration of calcium ion.The latent period,amplitude,duration of DAD and incidence of triggered activity were observed under a pre-treatment with different concentrations of NaHS (donor of H2S).The effects of glibenclamide,Bay K8644 and NG-nitro-L-arginine methyl ester (L-NAME) pretreatment on the actions of H2S were also studied.Results NaHS ( 100,200 μmoL/L) prolonged the latent period of DAD from( 12.0 ± 1.0) min to ( 19.9 ± 1.6) min ( P ＜ 0.05 ),( 23.7 ± 1.3 ) min ( P ＜ 0.01 ),decreased the altitude of DAD from ( 11.47 ±0.74) mV to (6.47 ±0.33) mY,(5.65 ±0.26) mV ( both P ＜0.01 ),shortened the duration of DAD from (205 ± 11 ) ms to ( 173 ± 10) ms and ( 134 ± 7 ) ms ( both P ＜ 0.05 ).The occurrence of triggered activity was inhibited from 5 samples to 4,2 and 1 sample in 6 samples.A pretreatment of adenosine triphosphate ( ATP)-sensitive potassium channel ( KATP ) blocker glibenclamide partially blocked the preventive effects of H2S on ouabain-induced DAD and triggered activity.The effects of H2S were completely blocked by L-type calcium channel agonist Bay K8644 (0.25 μmol/L).However a pretreatment of L-NAME ( 1 mmol/L),a nitric oxide (NO) synthase inhibitor,showed no effects on H2S.Conclusion H2S inhibits the ouabain-induced DAD and triggered activity in guinea pig papillary muscles.The opening of KATP channel with a reduced influx of calcium ion may be involved in the protective effects of H2S.