Ischemic preconditioning of single cardiac myocytes and the membrane currents involved

心脏具有防止局部缺血的保护机制。其中，缺血预处理是一个亮点。这种保护机制被认为是由内源性生物活性物质如腺苷、去甲肾上腺素、血管紧张素II和内皮细胞介导的。这些物质毫无例外地激活蛋白激酶C和百日咳毒素（PTX）敏感性GTP结合蛋白（Gi）。本研究旨在阐明内源性因子在缺血预适应中的作用。另一种心脏保护机制在新生儿心脏中是已知的，称为缺血耐受。我们还研究了腺苷对新生儿心肌细胞的影响，以阐明内在因素在新生儿心肌保护中的作用。我们首先检查是否短期缺氧或NaCN（1mM）灌注产生缺血预处理。我们的研究结果表明，短期缺血不诱导预适应效应。然而，腺苷的共同应用促进ATP敏感性钾电流的激活。因此，缺血预适应应归因于内在因素，而不是缺血本身。比较成年和新生心肌细胞，腺苷对新生心肌细胞I_2的抑制作用强<Ca>于成年心肌细胞。因此，这种药物被认为不仅有助于缺血预处理，而且有助于出生前后的缺血耐受。我们还研究了各种内在因素，这可能有助于心肌保护。我们发现前列腺素E1刺激EP受体或ATP刺激P2受体可引起穿孔敏感性G蛋白的刺激。因此，这些药物可能有助于成人细胞的IP或新生儿缺血耐受的缺血耐受。

The heart has protective mechanisms against ischemia. Among them, ischemic preconditiong is a high-light. This protecting mechanism has been proposed to be mediated by intrinsic bioactive agents, such as adenosine, norepinephrine, angiotensin II, and endothelia. These substances unexceptionably activate the protein kinase C and the pertussis toxin (PTX)-sensitive GTP-binding proteins (Gi). In this study, we aimed to clarify the roles of the intrinsic agents in the ischemic preconditioning. Another cardio-protective mechanism is known in new-born hearts, which is termed as ischemic tolerance. We also examined the effects of adenosine on neonate myocytes in order to elucidate the role of the intrinsic factors in the myocardial protection in neonates. We first examine whether or not short-term hypoxia or NaCN (1mM) perfusion produces the ischemic preconditioning. Our results suggest that short-term ischemia does not induce the preconditioning effects. However, co-application of adenosine facilitates the activation of the ATP-sensitive K current. Thus, the ischemic preconditioning should be attributable to the intrinsic factors, not to ischemia itself. When compared between adult and neonate myocytes, adenosine showed a more potent inhibition of I_<Ca> in neonate myocytes than in adult cells. Therefore, this agent is considered to contribute not only to ischemic preconditioning but also to ischemic tolerance around birth. We also examined various intrinsic factors, which may contribute to the myocardial protection. We found that the stimulation of EP receptor by prostaglandin E1 or P2 receptor stimulation by ATP causes the stimulation of the perrutsis-sensitive G protein. Thus, these agents may contribute to IP in adult cells or ischemic tolerance in neonate ischemic tolerance.