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机构地区:[1]中国医学科学院,中国协和医科大学药物研究所,北京100050
出 处:《生理学报》2006年第2期136-140,共5页Acta Physiologica Sinica
基 金:This work was supported by China Postdoctoral Science Foundationthe National Natural Science Foundation of China (No. 30371644) the National High Technology Research and Development Program (863) of China (No. 2004AA2Z3815).
摘 要:心肌缺血损伤过程中,胞内Na+、ATP及pH都出现明显变化。钠/钙交换对心肌细胞的钙平衡起重要的调节作用。本实验采用膜片钳全细胞记录豚鼠心室肌细胞钠/钙交换电流,研究温度和胞内Na+、ATP及pH对钠/钙交换双向电流的影响。结果表明,温度从22℃升至34℃,钠/钙交换电流增大约4倍,而pH值的改变对钠/钙交换双向电流没有明显的影响。在22-24℃时,同时耗竭胞内ATP和胞内酸化对钠/钙交换双向转运功能影响程度小;而在34-37℃时,同时耗竭胞内ATP和胞内酸化能抑制钠/钙交换双向电流的外向和内向成分,且内向成分抑制程度高于外向成分抑制程度。表明同时耗竭胞内ATP和胞内酸化对钠/钙交换的作用具有温度依赖性。胞内Na+超载能使钠/钙交换电流的外向成分增加, 但不增加或减少内向电流(即正向转运)成分。因此,胞内酸化及耗竭胞内ATP损伤细胞排钙机制和胞内钠超载通过钠/钙反向交换引起钙内流是引起心肌细胞钙超载的两个独立的重要因素。The Na^+-Ca^+ exchange is a major pathway for removal of cytosolic Ca^+ in cardiac myocytes. To explore the effects of temperature, intracellular Na^+, ATP and pH on Na^+-Ca^+ exchange currents (1NaSa) of intact guinea-pig myocytes, the whole-cell patchclamp technique was used to record I(Na/Ca) in isolated guinea-pig ventficular myocytes. We found that I(Na/Ca) at 34 ℃ was four times higher than that at 22 ℃. However, intracellular acidification had no obvious influence on bidirectional I(Na/Ca). At 22~24 ℃, intracellular ATP depletion and intracellular acidification did not markedly affect bidirectional I(Na/Ca) either. At 34~37 ℃. intracellular ATP depletion and intracellular acidification synergistically inhibited the outward and inward currents of I(Na/Ca), and blocked the inward currents of I(Na/Ca) more potently than the outward currents of 1N℃a. The effect of ATP on I(Na/Ca) is temperature-dependent. Intracellular higher sodium increased the outward currents of I(Na/Ca), however it didn't increase, even sometimes decreased the inward currents of I(Na/Ca). These results suggest that intracellular ATP depletion and intracellular acidification synergistically impair Ca^+ extrusion via forward mode Na+ -Ca2+ exchange, and intracellular sodium overload increases Ca^+ influx via reverse mode Na+-Ca^+ exchange, leading to calcium overload respectively.
分 类 号:R33[医药卫生—人体生理学]
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