Effects of overexpression of the Na$^+$-Ca$^2+$ exchanger
on Ca$^2+$i transients in murine ventricular myocytes.
Circ. Res. 82 (6): 657-65 (April 1998)
Abstract
We measured Ca$^2+$i and Na$^+$i in isolated transgenic
(TG) mouse myocytes overexpressing the Na$^+$-Ca$^2+$ exchanger
and in wild-type (WT) myocytes. In TG myocytes, the peak systolic
level and amplitude of electrically stimulated (ES) Ca$^2+$i
transients (0.25 Hz) were not significantly different from those
in WT myocytes, but the time to peak Ca$^2+$i was significantly
prolonged. The decline of ES Ca$^2+$i transients was significantly
accelerated in TG myocytes. The decline of a long-duration (4-s)
caffeine-induced Ca$^2+$i transient was markedly faster in
TG myocytes, and Na$^+$i was identical in TG and WT myocytes,
indicating that the overexpressed Na$^+$-Ca$^2+$ exchanger
is functionally active. The decline of a short-duration (100-ms)
caffeine-induced Ca$^2+$i transient in 0 Na$^+$/0 Ca$^2+$
solution did not differ between the two groups, suggesting that the
sarcoplasmic reticulum (SR) Ca$^2+$-ATPase function is not altered
by overexpression of the Na$^+$-Ca$^2+$ exchanger. There
was no difference in L-type Ca$^2+$ current density in WT and
TG myocytes. However, the sensitivity of ES Ca$^2+$i transients
to nifedipine was reduced in TG myocytes. This maintenance of Ca$^2+$i
transients in nifedipine was inhibited by Ni2+ and required SR Ca$^2+$
content, consistent with enhanced Ca$^2+$ influx by reverse Na$^+$-Ca$^2+$
exchange, and the resulting Ca$^2+$-induced Ca$^2+$ release
from SR. The rate of rise of Ca$^2+$i transients in nifedipine
in TG myocytes was much slower than when both the L-type Ca$^2+$
current and the Na$^+$-Ca$^2+$ exchange current function
together. In TG myocytes, action potential amplitude and action potential
duration at 50\% repolarization were reduced, and action potential
duration at 90\% repolarization was increased, relative to WT myocytes.
These data suggest that under these conditions, overexpression of
the Na$^+$-Ca$^2+$ exchanger in TG myocytes accelerates the
decline of Ca$^2+$i during relaxation, indicating enhanced
forward Na$^+$-Ca$^2+$ exchanger function. Increased Ca$^2+$
influx also appears to occur, consistent with enhanced reverse function.
These findings provide support for the physiological importance of
both these modes of Na$^+$-Ca$^2+$ exchange.
Description
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Links and resources
- URL:
- http://circres.ahajournals.org/cgi/content/full/82/6/657
- BibTeX key:
- Yao_1998_657
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