To investigate whether activity of the sarcolemmal Na pump modulates
the influence of sodium current on excitation-contraction (E-C) coupling,
we measured Ca$^2+$(i) transients (fluo-3) in single voltage-clamped
mouse ventricular myocytes (Na$^+$(pip) = 15 or 0 mM) when
the Na pump was activated (4.4 mM K$^+$(o)) and during abrupt
inhibition of the pump by exposure to 0 K with a rapid solution-switcher
device. After induction of steady state Ca$^2+$(i) transients
by conditioning voltage pulses (0.25 Hz), inhibition of the Na pump
for 1.5 s immediately before and continuing during a voltage pulse
(200 ms, -80 to 0 mV) caused a significant increase (15 +/- 2\%;
n = 16; p < 0.01) in peak systolic Ca$^2+$(i) when Na$^+$(pip)
was 15 mM. In the absence of sodium current (I(Na), which was blocked
by 60 microM tetrodotoxin (TTX)), inhibition of the Na pump immediately
before and during a voltage pulse did not result in an increase in
peak systolic Ca$^2+$(i). Abrupt blockade of I(Na) during a
single test pulse with TTX caused a slight decrease in peak Ca$^2+$(i),
whether the pump was active (9\%) or inhibited (10\%). With the reverse-mode
Na/Ca exchange inhibited by KB-R 7943, inhibition of the Na pump
failed to increase the magnitude of the peak systolic Ca$^2+$(i)
(4 +/- 1\%; p = NS) when Na$^+$(pip) was 15 mM. When Na$^+$(pip)
was 0 mM, the amplitude of the peak systolic Ca$^2+$(i) was
not altered by abrupt inhibition of the Na pump immediately before
and during a voltage pulse. These findings in adult mouse ventricular
myocytes indicate the Na pump can modulate the influence of I(Na)
on E-C coupling in a single beat and provide additional evidence
for the existence of Na fuzzy space, where Na$^+$ can significantly
modulate Ca$^2+$ influx via reverse Na/Ca exchange.
%0 Journal Article
%1 Su_2001_1230
%A Su, Z.
%A Sugishita, K.
%A Ritter, M.
%A Li, F.
%A Spitzer, K. W.
%A Barry, W. H.
%D 2001
%J Biophys. J.
%K , 11222287 ATPase, Animal, Animals, Arginine, BALB Barium Body C, C3H, Calcium Calcium, Cardiomyopathy, Cell Cells, Channels, Chlorides, Compounds, Contraction, Cultured, Cyclic Cytoskeleton, Diacetyl, Dilated, Disease Dyes, Enzyme Exchanger, Fluorescent GMP, Gov't, Graft Heart Heart, Homeostasis, Homologous, Inbred Inhibitors, Isoproterenol, Knockout, L-Type, Membrane Mice, Microfilaments, Models, Muscle Myocardial Myocardium, Nitric-Oxide Non-U.S. Organ P.H.S., Patch-Clamp Permeability, Potassium, Potentials, Proteins, Rejection, Resea, Research Reticulum, Sarcolemma, Sarcoplasmic Separation, Signaling, Size, Sodium, Sodium-Calcium Support, Synthase, Techniques, Tetrodotoxin, Thiourea, Transplantation, U.S. Ventricles, Weight, rch {N}a$^{+}$-{K}$^{+}$-Exchanging
%N 3
%P 1230--1237
%T The sodium pump modulates the influence of I(Na) on Ca$^2+$i
transients in mouse ventricular myocytes.
%U http://www.biophysj.org/cgi/content/full/80/3/1230
%V 80
%X To investigate whether activity of the sarcolemmal Na pump modulates
the influence of sodium current on excitation-contraction (E-C) coupling,
we measured Ca$^2+$(i) transients (fluo-3) in single voltage-clamped
mouse ventricular myocytes (Na$^+$(pip) = 15 or 0 mM) when
the Na pump was activated (4.4 mM K$^+$(o)) and during abrupt
inhibition of the pump by exposure to 0 K with a rapid solution-switcher
device. After induction of steady state Ca$^2+$(i) transients
by conditioning voltage pulses (0.25 Hz), inhibition of the Na pump
for 1.5 s immediately before and continuing during a voltage pulse
(200 ms, -80 to 0 mV) caused a significant increase (15 +/- 2\%;
n = 16; p < 0.01) in peak systolic Ca$^2+$(i) when Na$^+$(pip)
was 15 mM. In the absence of sodium current (I(Na), which was blocked
by 60 microM tetrodotoxin (TTX)), inhibition of the Na pump immediately
before and during a voltage pulse did not result in an increase in
peak systolic Ca$^2+$(i). Abrupt blockade of I(Na) during a
single test pulse with TTX caused a slight decrease in peak Ca$^2+$(i),
whether the pump was active (9\%) or inhibited (10\%). With the reverse-mode
Na/Ca exchange inhibited by KB-R 7943, inhibition of the Na pump
failed to increase the magnitude of the peak systolic Ca$^2+$(i)
(4 +/- 1\%; p = NS) when Na$^+$(pip) was 15 mM. When Na$^+$(pip)
was 0 mM, the amplitude of the peak systolic Ca$^2+$(i) was
not altered by abrupt inhibition of the Na pump immediately before
and during a voltage pulse. These findings in adult mouse ventricular
myocytes indicate the Na pump can modulate the influence of I(Na)
on E-C coupling in a single beat and provide additional evidence
for the existence of Na fuzzy space, where Na$^+$ can significantly
modulate Ca$^2+$ influx via reverse Na/Ca exchange.
@article{Su_2001_1230,
abstract = {To investigate whether activity of the sarcolemmal Na pump modulates
the influence of sodium current on excitation-contraction (E-C) coupling,
we measured [{C}a$^{2+}$](i) transients (fluo-3) in single voltage-clamped
mouse ventricular myocytes ([{N}a$^{+}$](pip) = 15 or 0 mM) when
the Na pump was activated (4.4 mM {K}$^{+}$(o)) and during abrupt
inhibition of the pump by exposure to 0 K with a rapid solution-switcher
device. After induction of steady state [{C}a$^{2+}$](i) transients
by conditioning voltage pulses (0.25 Hz), inhibition of the Na pump
for 1.5 s immediately before and continuing during a voltage pulse
(200 ms, -80 to 0 mV) caused a significant increase (15 +/- 2\%;
n = 16; p < 0.01) in peak systolic [{C}a$^{2+}$](i) when [{N}a$^{+}$](pip)
was 15 mM. In the absence of sodium current (I(Na), which was blocked
by 60 microM tetrodotoxin ({TTX})), inhibition of the Na pump immediately
before and during a voltage pulse did not result in an increase in
peak systolic [{C}a$^{2+}$](i). Abrupt blockade of I(Na) during a
single test pulse with {TTX} caused a slight decrease in peak [{C}a$^{2+}$](i),
whether the pump was active (9\%) or inhibited (10\%). With the reverse-mode
Na/Ca exchange inhibited by {KB}-R 7943, inhibition of the Na pump
failed to increase the magnitude of the peak systolic [{C}a$^{2+}$](i)
(4 +/- 1\%; p = {NS}) when [{N}a$^{+}$](pip) was 15 mM. When [{N}a$^{+}$](pip)
was 0 mM, the amplitude of the peak systolic [{C}a$^{2+}$](i) was
not altered by abrupt inhibition of the Na pump immediately before
and during a voltage pulse. These findings in adult mouse ventricular
myocytes indicate the Na pump can modulate the influence of I(Na)
on E-C coupling in a single beat and provide additional evidence
for the existence of Na fuzzy space, where [{N}a$^{+}$] can significantly
modulate {C}a$^{2+}$ influx via reverse Na/Ca exchange.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Su, Z. and Sugishita, K. and Ritter, M. and Li, F. and Spitzer, K. W. and Barry, W. H.},
biburl = {https://www.bibsonomy.org/bibtex/20306dbb9b46ea79e00b2de92a6158e02/hake},
description = {The whole bibliography file I use.},
file = {Su_2001_1230.pdf:Su_2001_1230.pdf:PDF},
interhash = {f4cbe4dc2a4849c93030eee2683da475},
intrahash = {0306dbb9b46ea79e00b2de92a6158e02},
journal = {Biophys. J.},
key = 134,
keywords = {, 11222287 ATPase, Animal, Animals, Arginine, BALB Barium Body C, C3H, Calcium Calcium, Cardiomyopathy, Cell Cells, Channels, Chlorides, Compounds, Contraction, Cultured, Cyclic Cytoskeleton, Diacetyl, Dilated, Disease Dyes, Enzyme Exchanger, Fluorescent GMP, Gov't, Graft Heart Heart, Homeostasis, Homologous, Inbred Inhibitors, Isoproterenol, Knockout, L-Type, Membrane Mice, Microfilaments, Models, Muscle Myocardial Myocardium, Nitric-Oxide Non-U.S. Organ P.H.S., Patch-Clamp Permeability, Potassium, Potentials, Proteins, Rejection, Resea, Research Reticulum, Sarcolemma, Sarcoplasmic Separation, Signaling, Size, Sodium, Sodium-Calcium Support, Synthase, Techniques, Tetrodotoxin, Thiourea, Transplantation, U.S. Ventricles, Weight, rch {N}a$^{+}$-{K}$^{+}$-Exchanging},
month = Mar,
number = 3,
pages = {1230--1237},
pmid = {11222287},
timestamp = {2009-06-03T11:21:33.000+0200},
title = {The sodium pump modulates the influence of I(Na) on [{C}a$^{2+}$]i
transients in mouse ventricular myocytes.},
url = {http://www.biophysj.org/cgi/content/full/80/3/1230},
volume = 80,
year = 2001
}