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$^+$-Ca$^2+$
exchangers (NCX) could enhance Ca$^2+$ influx via NCX (and Ca$^2+$-induced
Ca$^2+$ release). We tested whether INa could increase Na$^+$sm,
using NCX current (INCX) as a biosensor in rabbit ventricular myocytes
(with Ca$^2+$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.
%0 Journal Article
%1 Webe_2003_950
%A Weber, Christopher R
%A Ginsburg, Kenneth S
%A Bers, Donald M
%D 2003
%J Circ. Res.
%K 12702644 Action Allosteric Animals, Calcium, Cardiac, Cell Cells, Conductivity, Congestive, Contraction, Cultured, Electric Electrophysiology, Exchanger, Failure, Gov't, Heart Humans, Ion Ions, Kinetics, Membrane, Myocardial Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rabbits, Regulation, Research Separation, Sodium, Sodium-Calcium Support, Techniques, Transport, U.S.
%N 9
%P 950--952
%R 8.7F
%T Cardiac submembrane Na$^+$ transients sensed by Na$^+$-Ca$^2+$
exchange current.
%U http://dx.doi.org/8.7F
%V 92
%X 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$^+$-Ca$^2+$
exchangers (NCX) could enhance Ca$^2+$ influx via NCX (and Ca$^2+$-induced
Ca$^2+$ release). We tested whether INa could increase Na$^+$sm,
using NCX current (INCX) as a biosensor in rabbit ventricular myocytes
(with Ca$^2+$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.
@article{Webe_2003_950,
abstract = {{N}a$^{+}$ influx via INa during cardiac action potentials can raise
bulk [{N}a$^{+}$]i by 10 to 15 micromol/L. However, larger rises
in submembrane [{N}a$^{+}$] ([{N}a$^{+}$]sm) local to {N}a$^{+}$-{C}a$^{2+}$
exchangers (NCX) could enhance {C}a$^{2+}$ influx via NCX (and {C}a$^{2+}$-induced
{C}a$^{2+}$ release). We tested whether INa could increase [{N}a$^{+}$]sm,
using NCX current (INCX) as a biosensor in rabbit ventricular myocytes
(with [{C}a$^{2+}$]i buffered, [{N}a$^{+}$]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 [{N}a$^{+}$]i), INCX shifted outward. At 5 ms and +100
mV, INa shifted INCX outward by 0.23 A/F (corresponding to Delta[{N}a$^{+}$]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[{N}a$^{+}$]sm during INa
may be 60 times higher than bulk Delta[{N}a$^{+}$]i.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Weber, Christopher R and Ginsburg, Kenneth S and Bers, Donald M},
biburl = {https://www.bibsonomy.org/bibtex/260b9e278d005f7f4b1db3cf8222b99d5/hake},
description = {The whole bibliography file I use.},
doi = {8.7F},
file = {Webe_2003_950.pdf:Webe_2003_950.pdf:PDF},
interhash = {5a043c56eac637dc7915105858031f00},
intrahash = {60b9e278d005f7f4b1db3cf8222b99d5},
journal = {Circ. Res.},
key = 149,
keywords = {12702644 Action Allosteric Animals, Calcium, Cardiac, Cell Cells, Conductivity, Congestive, Contraction, Cultured, Electric Electrophysiology, Exchanger, Failure, Gov't, Heart Humans, Ion Ions, Kinetics, Membrane, Myocardial Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rabbits, Regulation, Research Separation, Sodium, Sodium-Calcium Support, Techniques, Transport, U.S.},
month = May,
number = 9,
pages = {950--952},
pii = {01.RES.0000071747.61468.7F},
pmid = {12702644},
timestamp = {2009-06-03T11:21:36.000+0200},
title = {Cardiac submembrane [{N}a$^{+}$] transients sensed by {N}a$^{+}$-{C}a$^{2+}$
exchange current.},
url = {http://dx.doi.org/8.7F},
volume = 92,
year = 2003
}