Kohomoto O, Levi A J, Bridge J H
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City 84112.
Circ Res. 1994 Mar;74(3):550-4. doi: 10.1161/01.res.74.3.550.
Exchange-inhibitory peptide (XIP) can inhibit sodium-calcium exchange without inhibiting L-type calcium current (ICa). We therefore used this compound to test the hypothesis that reverse sodium-calcium exchange can trigger contraction in guinea pig ventricular myocytes. When cells were dialyzed with 20 mmol/L sodium, rapid blockade of ICa with nifedipine had little effect on cell shortening. However, if reverse exchange was inhibited by first dialyzing the cells with XIP, blockade of ICa largely inhibited cell shortening. In cells dialyzed with 10 mmol/L sodium, about 51% of the maximum cell shortening remained after ICa was blocked. When both ICa and reverse exchange were significantly inhibited with nifedipine and XIP, only 24% of the cell shortening remained; ie, 27% was XIP inhibitable. Cells dialyzed with solutions deficient in sodium exhibited contractions that were largely dependent on ICa (ie, not XIP inhibitable). If the sarcoplasmic reticulum (SR) was disabled with ryanodine and thapsigargin, reverse exchange could not cause contraction. We therefore conclude that with intact SR, reverse sodium-calcium exchange activates contraction by triggering calcium release from the SR in cells dialyzed with either 10 or 20 mmol/L sodium. A scrambled sequence of XIP, sXIP, caused no measurable effect on contraction.
交换抑制肽（XIP）可抑制钠钙交换而不抑制L型钙电流（ICa）。因此，我们使用该化合物来检验以下假设：反向钠钙交换可引发豚鼠心室肌细胞的收缩。当用20 mmol/L钠透析细胞时，用硝苯地平快速阻断ICa对细胞缩短影响不大。然而，如果先用XIP透析细胞以抑制反向交换，阻断ICa则会很大程度上抑制细胞缩短。在用10 mmol/L钠透析的细胞中，阻断ICa后仍保留约51%的最大细胞缩短。当用硝苯地平和XIP显著抑制ICa和反向交换时，仅保留24%的细胞缩短；即，27%是XIP可抑制的。用缺钠溶液透析的细胞表现出的收缩很大程度上依赖于ICa（即，不受XIP抑制）。如果用兰尼碱和毒胡萝卜素使肌浆网（SR）失活，反向交换则不能引起收缩。因此，我们得出结论，在SR完整的情况下，反向钠钙交换通过触发用10或20 mmol/L钠透析细胞时SR释放钙来激活收缩。XIP的乱序序列sXIP对收缩没有可测量的影响。
