title: Cardiac submembrane [Na+] transients sensed by Na+-Ca2+ exchange current.
abstract: 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 Delta[Na+]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 Delta[Na+]sm during INa may be 60 times higher than bulk Delta[Na+]i.
authors.affiliation: Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Ave, Maywood, Ill 60153, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Weber
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Ginsburg
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000200:Action Potentials; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004553:Electric Conductivity; D007477:Ions; D007700:Kinetics; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012964:Sodium / Q000032:analysis*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
chemical_list: D007477:Ions; D019831:Sodium-Calcium Exchanger; D012964:Sodium