Cardiac Submembrane [Na+] Transients Sensed by Na+-Ca2+ Exchange Current

Na influx via INa during cardiac action potentials can raise bulk [Na]i by 10 to 15 μmol/L. However, larger rises in submembrane [Na] ([Na]sm) local to Na-Ca exchangers (NCX) could enhance Ca influx via NCX (and Ca-induced Ca release). We tested whether INa could increase [Na]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca]i buffered, [Na]i=10 mmol/L, and other currents blocked). We measured INCX as early as 5 ms after INa. Prior INa activation did not affect INCX at physiological membrane potentials (Em=−100 to +50 mV), but for Em >+50 mV (where INCX is especially sensitive to [Na]i), INCX shifted outward. At 5 ms and +100 mV, INa shifted INCX outward by 0.23 A/F (corresponding to Δ[Na]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of ≈15 ms. Thus, the impact of INa on NCX is almost undetectable at physiological Em and short lived. This suggests that INa effects on excitation-contraction coupling (via outward INCX) are minimal and limited to early during the action potential. However, local Δ[Na]sm during INa may be 60 times higher than bulk Δ[Na]i.