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 (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.
Kohomoto
O
O
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City 84112.
Levi
A J
AJ
Bridge
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006352:Heart Ventricles; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D002352:Carrier Proteins; D010455:Peptides; D019831:Sodium-Calcium Exchanger; D013729:Terpenes; C066745:exchanger inhibitory peptide; D012433:Ryanodine; D019284:Thapsigargin; D009543:Nifedipine; D002118:Calcium