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(Circulation Research. 2003;92:950.)
© 2003 American Heart Association, Inc.

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

Christopher R. Weber, Kenneth S. Ginsburg, Donald M. Bers

From the Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill.

Correspondence to Donald M. Bers, PhD, Department of Physiology, Loyola University Chicago, 2160 South First Ave, Maywood, IL 60153. E-mail dbers{at}lumc.edu

Abstract

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 [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 [Na⁺]_sm during I_Na may be 60 times higher than bulk [Na⁺]_i.

Key Words: Na⁺ current • excitation-contraction coupling

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