EXTRACELLULAR OSMOTIC-PRESSURE MODULATES SODIUM-CALCIUM EXCHANGE IN ISOLATED GUINEA-PIG VENTRICULAR MYOCYTES

1. The sensitivity of the cardiac Na+-Ca2+ exchange current to changes in osmotic pressure was investigated in guinea-pig ventricular myocyt es, using the whole-cell patch-clamp technique. 2. A hyposmotic challe nge applied by removal of sucrose from the standard bathing solution r educed exchanger current, measured as the Ni2+-sensitive component of whole-cell trans-sarcolemmal current. These changes were fully reversi ble. 3. No response of whole-cell current to hyposmosis was observed w hen Ca2+ was removed from the bathing solution by chelation with 1 mM EGTA. 4. Inclusion of 25 mu M exchanger inhibitory peptide (XIP) in th e pipette solution caused a marked reduction in the Ni2+-sensitive com ponent of membrane current, but the percentage change in Ni2+-sensitiv e membrane slope conductance evoked by hyposmosis was the same as when XIP was omitted from the pipette solution. 5. Exposure of cells to hy perosmotic solutions produced variable responses. In a majority of cel ls, solutions 30% hyperosmotic compared with control evoked a persiste nt increase in exchanger current, whereas for solutions 50% hyperosmot ic, a larger but transient increase in current was observed. 6. Over a wide range of osmolalities (50-130% of isosmotic) the changes in Ni2-sensitive membrane slope conductance were Linearly related to the cha nges in extracellular osmotic pressure. 7. We propose that one consequ ence of exposing ventricular myocytes to anisosmotic solutions is modu lation of Na+-Ca2+ exchange current.