Nottingham Trent University, Nottingham, UK.
Can J Physiol Pharmacol. 2011 Jan;89(1):24-30. doi: 10.1139/y10-106.
Ischaemic postconditioning is a phenomenon whereby short periods of ischaemia applied during the start of reperfusion protect the myocardium from the damaging consequences of reperfusion. As such, pharmacological-induced postconditioning represents an attractive therapeutic strategy for reducing reperfusion injury during cardiac surgery and following myocardial infarction. The primary aim of this study was to determine the role of large-conductance Ca²(+)-activated potassium channels (BK(Ca) channels) in adenosine A₁ receptor-induced pharmacological postconditioning in the rat embryonic cardiomyoblast-derived cell line H9c2. H9c2 cells were exposed to 6 h hypoxia (0.5% O₂) followed by 18 h reoxygenation (H/R) after which cell viability was assessed by monitoring lactate dehydrogenase (LDH) release and caspase-3 activation. The adenosine A₁ receptor agonist N⁶-cyclopentyladenosine (CPA; 100 nmol/L) or the BK(Ca) channel opener NS1619 (10 µmol/L) were added for 30 min at the start of reoxygenation following 6 h hypoxic exposure. Where appropriate, cells were treated (15 min) before pharmacological postconditioning with the BK(Ca) channel blockers paxilline (1 µmol/L) or iberiotoxin (100 nmol/L). Pharmacological postconditioning with CPA or NS1619 significantly reduced H/R-induced LDH release. Treatment with paxilline or iberiotoxin attenuated adenosine A₁ receptor and NS1619-induced pharmacological postconditioning. These results have shown for the first time that BK(Ca) channels are involved in adenosine A₁ receptor-induced pharmacological postconditioning in a cell model system.
缺血后处理是一种现象，即在再灌注开始时施加短暂的缺血期可保护心肌免受再灌注损伤的有害后果。因此，药理学诱导的后处理代表了一种有吸引力的治疗策略，可减少心脏手术中和心肌梗死后的再灌注损伤。本研究的主要目的是确定大电导钙激活钾通道（BK（Ca）通道）在腺苷 A₁ 受体诱导的大鼠胚胎心肌细胞源性细胞系 H9c2 中的药理学后处理中的作用。H9c2 细胞暴露于 6 小时缺氧（0.5% O₂）后，再进行 18 小时复氧（H/R），然后通过监测乳酸脱氢酶（LDH）释放和 caspase-3 激活来评估细胞活力。在 6 小时缺氧暴露后复氧开始时添加腺苷 A₁ 受体激动剂 N⁶-环戊基腺苷（CPA；100 nmol/L）或 BK（Ca）通道 opener NS1619（10 µmol/L）30 分钟。在进行药理学后处理之前，如果合适，细胞用 BK（Ca）通道阻滞剂 paxilline（1 µmol/L）或 iberiotoxin（100 nmol/L）处理（15 分钟）。CPA 或 NS1619 的药理学后处理可显著降低 H/R 诱导的 LDH 释放。用 paxilline 或 iberiotoxin 处理可减弱腺苷 A₁ 受体和 NS1619 诱导的药理学后处理。这些结果首次表明，BK（Ca）通道参与了细胞模型系统中腺苷 A₁ 受体诱导的药理学后处理。
