We investigate cardiac excitation-contraction coupling in the absence
of sarcolemmal Na$^+$ - Ca$^2+$ exchange using NCX1 knock
out mice. Knock out of NCX1 is embryonic lethal, and we measure Ca$^2+$
transients and contractions in heart tubes from embryos at day 9.5
post coitum. Immunoblot and electron microscopy both indicate that
sarcoplasmic reticular membranes are diminished in the knock out
(NCX(-/-)) heart tubes. Both Ni$^2+$ and nifedipine block excitation-contraction
coupling in NCX-containing (NCX+) and NCX(-/-) heart tubes indicating
an essential role for the L-type Ca$^2+$ current. Under basal
conditions (1Hz stimulation), the NCX(-/-) heart tubes have normal
Ca$^2+$ transients but are unable to maintain homeostasis when
Ca$^2+$ fluxes are increased by various interventions (increased
stimulation frequency, caffeine, isoproterenol). In each case, the
NCX(-/-) heart tubes respond to the intervention in a more deleterious
manner (increased diastolic Ca$^2+$, decreased Ca$^2+$ transient)
than the NCX+ heart tubes. Expression of the sarcolemmal Ca$^2+$
pump was not upregulated. The sarcolemmal Ca$^2+$ pump, however,
was able to compensate surprisingly well for the absence of Na$^+$
- Ca$^2+$ exchange under basal conditions.
%0 Journal Article
%1 Reut_2003_19
%A Reuter, Hannes
%A Henderson, Scott A
%A Han, Tieyan
%A Mottino, Giuliano A
%A Frank, Joy S
%A Ross, Robert S
%A Goldhaber, Joshua I
%A Philipson, Kenneth D
%D 2003
%J Cell Calcium
%K 12767889 ATPase, Action Adaptation, Animals, Blockers, Caffeine, Calcium Calcium, Cardiac, Channel Channels, Contraction, Culture Deletion, Echocardiography, Electron, Exchanger, Exons, Female, Fetal Fetus, Gene Gov't, Heart, Integrases, Intracellular Isoproterenol, Knockout, L-Type, Male, Membranes, Mice, Microscopy, Models, Molecular, Myocardial Myocardium, Myocytes, Non-U.S. Organ P.H.S., Patch-Clamp Physiological, Potentials, Proteins, Research Reticulum, Sarcoplasmic Sequence Signaling, Sodium, Sodium-Calcium Support, Targeting, Techniques, U.S. Viral {C}a$^{2+}$-Transporting
%N 1
%P 19-26
%T Cardiac excitation-contraction coupling in the absence of Na$^+$
- Ca$^2+$ exchange.
%U http://dx.doi.org/10.1016/S0143-4160(03)00018-6
%V 34
%X We investigate cardiac excitation-contraction coupling in the absence
of sarcolemmal Na$^+$ - Ca$^2+$ exchange using NCX1 knock
out mice. Knock out of NCX1 is embryonic lethal, and we measure Ca$^2+$
transients and contractions in heart tubes from embryos at day 9.5
post coitum. Immunoblot and electron microscopy both indicate that
sarcoplasmic reticular membranes are diminished in the knock out
(NCX(-/-)) heart tubes. Both Ni$^2+$ and nifedipine block excitation-contraction
coupling in NCX-containing (NCX+) and NCX(-/-) heart tubes indicating
an essential role for the L-type Ca$^2+$ current. Under basal
conditions (1Hz stimulation), the NCX(-/-) heart tubes have normal
Ca$^2+$ transients but are unable to maintain homeostasis when
Ca$^2+$ fluxes are increased by various interventions (increased
stimulation frequency, caffeine, isoproterenol). In each case, the
NCX(-/-) heart tubes respond to the intervention in a more deleterious
manner (increased diastolic Ca$^2+$, decreased Ca$^2+$ transient)
than the NCX+ heart tubes. Expression of the sarcolemmal Ca$^2+$
pump was not upregulated. The sarcolemmal Ca$^2+$ pump, however,
was able to compensate surprisingly well for the absence of Na$^+$
- Ca$^2+$ exchange under basal conditions.
@article{Reut_2003_19,
abstract = {We investigate cardiac excitation-contraction coupling in the absence
of sarcolemmal {N}a$^{+}$ - {C}a$^{2+}$ exchange using NCX1 knock
out mice. Knock out of NCX1 is embryonic lethal, and we measure {C}a$^{2+}$
transients and contractions in heart tubes from embryos at day 9.5
post coitum. Immunoblot and electron microscopy both indicate that
sarcoplasmic reticular membranes are diminished in the knock out
(NCX(-/-)) heart tubes. Both {N}i$^{2+}$ and nifedipine block excitation-contraction
coupling in NCX-containing (NCX+) and NCX(-/-) heart tubes indicating
an essential role for the L-type {C}a$^{2+}$ current. Under basal
conditions (1Hz stimulation), the NCX(-/-) heart tubes have normal
{C}a$^{2+}$ transients but are unable to maintain homeostasis when
{C}a$^{2+}$ fluxes are increased by various interventions (increased
stimulation frequency, caffeine, isoproterenol). In each case, the
NCX(-/-) heart tubes respond to the intervention in a more deleterious
manner (increased diastolic {C}a$^{2+}$, decreased {C}a$^{2+}$ transient)
than the NCX+ heart tubes. Expression of the sarcolemmal {C}a$^{2+}$
pump was not upregulated. The sarcolemmal {C}a$^{2+}$ pump, however,
was able to compensate surprisingly well for the absence of {N}a$^{+}$
- {C}a$^{2+}$ exchange under basal conditions.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Reuter, Hannes and Henderson, Scott A and Han, Tieyan and Mottino, Giuliano A and Frank, Joy S and Ross, Robert S and Goldhaber, Joshua I and Philipson, Kenneth D},
biburl = {https://www.bibsonomy.org/bibtex/2c89a796b38a1875f93c78bfd87dc82e0/hake},
description = {The whole bibliography file I use.},
file = {Reut_2003_19.pdf:Reut_2003_19.pdf:PDF},
interhash = {6cba93655d27f3ee808aa9f9db727fc7},
intrahash = {c89a796b38a1875f93c78bfd87dc82e0},
journal = {Cell Calcium},
keywords = {12767889 ATPase, Action Adaptation, Animals, Blockers, Caffeine, Calcium Calcium, Cardiac, Channel Channels, Contraction, Culture Deletion, Echocardiography, Electron, Exchanger, Exons, Female, Fetal Fetus, Gene Gov't, Heart, Integrases, Intracellular Isoproterenol, Knockout, L-Type, Male, Membranes, Mice, Microscopy, Models, Molecular, Myocardial Myocardium, Myocytes, Non-U.S. Organ P.H.S., Patch-Clamp Physiological, Potentials, Proteins, Research Reticulum, Sarcoplasmic Sequence Signaling, Sodium, Sodium-Calcium Support, Targeting, Techniques, U.S. Viral {C}a$^{2+}$-Transporting},
month = Jul,
number = 1,
pages = {19-26},
pii = {S0143416003000186},
timestamp = {2009-06-03T11:21:26.000+0200},
title = {Cardiac excitation-contraction coupling in the absence of {N}a$^{+}$
- {C}a$^{2+}$ exchange.},
url = {http://dx.doi.org/10.1016/S0143-4160(03)00018-6},
volume = 34,
year = 2003
}