RELATION BETWEEN REVERSE SODIUM-CALCIUM EXCHANGE AND SARCOPLASMIC-RETICULUM CALCIUM-RELEASE IN GUINEA-PIG VENTRICULAR CELLS

Exchange-inhibitory peptide (XIP) can inhibit sodium-calcium exchange without inhibiting L-type calcium current (I-Ca). 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 I-Ca with nifedipine had little effect on cell shortening. However, if reverse exchange was inhibited by first dialyzing the cells with XIP, blockade of I-Ca largely inhibited cell shortening. In cells dialyzed with 10 mmol/L sodium, about 51% of the maximum cell shortening remained after I, was blocked. When both I-Ca and reverse exchange were significantly inhibited with nifedipine and XIP, only 24% of the cell shortening remained; ie, 27% was XIP inhabitable. Cells dialyzed with solutions deficient in sodium exhibited contractions that were largely dependent on I-Ca (ie, not XIP inhabitable). 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.