Prior INa activation shifted INCX outward by 0.23 A/F at +100 mV, corresponding to a local submembrane Na+ increase of 0.24 mmol/L, but effects were undetectable at physiological membrane potentials.
Na+ influx via INa during cardiac action potentials can raise bulk Na+i by 10 to 15 micromol/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 INa could increase Na+sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with Ca2+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 DeltaNa+sm=0.24 mmol/L). The effect of INa dissipated with a time constant of approximately 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 DeltaNa+sm during INa may be 60 times higher than bulk DeltaNa+i.
Weber et al. (Thu,) reported a other. INa activation vs. No prior INa activation / physiological membrane potentials was evaluated on NCX current (INCX) shift. Prior INa activation shifted INCX outward by 0.23 A/F at +100 mV, corresponding to a local submembrane Na+ increase of 0.24 mmol/L, but effects were undetectable at physiological membrane potentials.
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