Abstract
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.
- 12767889
- action
- adaptation,
- animals,
- atpase,
- 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
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