Cardiac submembrane [Na⁺] transients sensed by Na⁺-Ca²⁺ exchange current

Na⁺ influx via I_Na 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⁺-Ca²⁺ exchangers (NCX) could enhance Ca²⁺ influx via NCX (and Ca²⁺-induced Ca²⁺ release). We tested whether I_Na could increase [Na⁺]_sm, using NCX current (I_NCX) as a biosensor in rabbit ventricular myocytes (with [Ca²⁺]_i buffered, [Na⁺]_i = 10 mmol/L, and other currents blocked). We measured I_NCX as early as 5 ms after I_Na. Prior I_Na activation did not affect I_NCX at physiological membrane potentials (E_m = -100 to +50 mV), but for E_m >+50 mV (where I_NCX is especially sensitive to [Na⁺]_i), I_NCX shifted outward. At 5 ms and +100 mV, I_Na shifted I_NCX outward by 0.23 A/F (corresponding to Δ[Na⁺]_sm=0.24 mmol/L). The effect of I_Na dissipated with a time constant of ≈15 ms. Thus, the impact of I_Na on NCX is almost undetectable at physiological E_m and short lived. This suggests that I_Na effects on excitation-contraction coupling (via outward I_NCX) are minimal and limited to early during the action potential. However, local Δ[Na⁺]_sm during I_Na may be 60 times higher than bulk Δ[Na⁺]_i.