温度和胞内钠、ATP及酸碱度对心室肌细胞钠钙交换电流的调节
周红义, 韩重阳, 王晓良
医科院、中国协和医科大学药物研究所.北京 100050
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。该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。
Regulative effects of temperature, intracellular sodium, ATP and pH on I_(Na/Ca) of cardiac myocytes
Zhou Hongyi, Han Chongyang, Wang Xiaoliang
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.Beijing 100050
Abstract
The Na~(+)-Ca~(2+) exchange is a major pathway for removal of cytosolic Ca~(2+) in cardiac myocytes. To explore the effects of temperature, intracellular Na~(+), ATP and pH on Na~(+)-Ca~(2+) exchange currents (I_(Na/Ca)) 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 I_(Na/Ca). 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~(2+) extrusion via forward mode Na~(+)-Ca~(2+) exchange, and intracellular sodium overload increases Ca~(2+) influx via reverse mode Na~(+)-Ca~(2+) exchange, leading to calcium overload respectively.
Key words: sodium-calcium exchanger;Temperature;sodium;patch-clamp technique
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引用本文:
周红义, 韩重阳, 王晓良. 温度和胞内钠、ATP及酸碱度对心室肌细胞钠钙交换电流的调节[J]. 生理学报 2006; 58 (2): .
Zhou Hongyi, Han Chongyang, Wang Xiaoliang. Regulative effects of temperature, intracellular sodium, ATP and pH on I_(Na/Ca) of cardiac myocytes. Acta Physiol Sin 2006; 58 (2): (in Chinese with English abstract).