Intracellular acidosis decreases the outward Na⁺-Ca²⁺ exchange current in guinea pig ventricular myocytes

The Na⁺-Ca²⁺ exchange transport operating in outward mode has been suggested to cause Ca²⁺ entry during reperfusion or reoxygenation, exchanging extracellular Ca²⁺ for intracellular Na⁺ that has accumulated during ischemia or cardioplegia. During cardioplegia, however, an increase in Ca²⁺ entry via this mechanism can be decreased due to increased intracellular H⁺ activity and a decrease in cellular ATP content. In this study giant excised cardiac sarcolemmal membrane patch clamp technique was employed to investigate the effect of cytosolic pH change on the Na⁺-Ca²⁺ exchanger, excluding the effect of ATP, in guinea pig cardiac myocytes. The outward Na⁺-dependent current, which has a characteristics of Hill equation, was decreased as pH was decreased in the range of 7.5-6.5. The current density generated by the Na⁺-Ca²⁺ exchange transport was 56.6 ± 4.4 pA/pF (Mean ± S.E.M.) at pH 7.2 and decreased to 42.9 ± 3.0 pA/pF at pH 6.9. These results imply that Na⁺-Ca²⁺ exchange transport, operating in a reverse mode during cardioplegia, decreases due to increased intracellular H⁺, and further suggest that consequent intracellular Na⁺ accumulation is one of aggravating factors for Ca²⁺ influx during reoxygenation or reperfusion.