Stadnicka Anna, Marinovic Jasna, Bienengraeber Martin, Bosnjak Zeljko J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Anesthesiology. 2006 Mar;104(3):503-10. doi: 10.1097/00000542-200603000-00018.
The early memory of anesthetic-induced preconditioning (APC) is a period when myocardial protection continues even after removal of the anesthetic. Because adenosine triphosphate-sensitive potassium (KATP) channels are important mediators of APC, the authors investigated the hypothesis that the memory involves channel priming by isoflurane via a long-term modulation of the sensitivity to intracellular adenosine nucleotides.
Ventricular cardiomyocytes were obtained from the rat hearts after 30 min in vivo APC with 1.4% isoflurane and from control non-APC rat hearts. Whole cell and excised inside-out patch clamp techniques were used to study the sarcolemmal KATP channel. Membrane expression of KATP channel proteins, the pore-forming inward rectifier Kir6.2, and the regulatory sulfonylurea receptor SUR2A were assessed in APC and non-APC hearts by Western blotting.
Activation of whole cell KATP current by isoflurane was enhanced after in vivo APC. At the single-channel level, this was paralleled by a 12-fold decrease in adenosine 5'-triphosphate sensitivity and a 3-fold decrease in adenosine 5'-diphosphate sensitivity, without changing the probability of channel opening or single-channel conductance. The membrane expression of Kir6.2 and SUR2A subunits was not altered by in vivo APC. A direct in vitro application of isoflurane to excised membrane patches increased the channel open probability and produced a 4-fold decrease in adenosine 5'-triphosphate sensitivity only of channels in non-APC myocytes.
In vivo APC by isoflurane decreases sensitivity of the sarcolemmal KATP channel to inhibition by adenosine 5'-triphosphate and decreases adenosine 5'-diphosphate sensitivity. These effects persist even after discontinuation of the anesthetic, suggesting a possible novel factor that may contribute to the mechanism of early memory of APC.
麻醉诱导预处理（APC）的早期记忆是指即使在去除麻醉剂后心肌保护仍持续的一段时间。由于三磷酸腺苷敏感性钾（KATP）通道是APC的重要介质，作者研究了以下假设：这种记忆涉及异氟烷通过对细胞内腺苷核苷酸敏感性的长期调节来使通道致敏。
在体用1.4%异氟烷进行30分钟APC后，从大鼠心脏获取心室心肌细胞，并从对照非APC大鼠心脏获取心肌细胞。采用全细胞和膜片外翻式膜片钳技术研究肌膜KATP通道。通过蛋白质印迹法评估APC和非APC心脏中KATP通道蛋白、形成孔道的内向整流钾通道Kir6.2和调节性磺脲类受体SUR2A的膜表达。
在体APC后，异氟烷对全细胞KATP电流的激活增强。在单通道水平，这伴随着三磷酸腺苷敏感性降低12倍和二磷酸腺苷敏感性降低3倍，而通道开放概率或单通道电导未改变。Kir6.2和SUR2A亚基的膜表达未因在体APC而改变。将异氟烷直接体外应用于分离的膜片，仅增加了非APC心肌细胞中通道的开放概率，并使三磷酸腺苷敏感性降低4倍。
异氟烷在体APC降低了肌膜KATP通道对三磷酸腺苷抑制的敏感性，并降低了二磷酸腺苷敏感性。即使在停用麻醉剂后，这些效应仍持续存在，提示可能存在一个新的因素，它可能参与了APC早期记忆的机制。
