Cmn. Terracciano et al., Overexpression of the Na+/Ca2+ exchanger and inhibition of the sarcoplasmic reticulum Ca2+-ATPase in ventricular myocytes from transgenic mice, CARDIO RES, 49(1), 2001, pp. 38-47
Citations number
37
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background: Myocytes from failing hearts produce slower and smaller Ca2+ tr
ansients associated with reduction in expression of sarcoplasmic reticulum
(SR) Ca2+ ATPase and an overexpression of Na+/Ca2+ exchanger. Since the phy
siological role of both these proteins is competing for, and removing, Ca2 from the cytoplasm, overexpression of the exchanger may compensate for les
s effective SR Ca2+ uptake. This study demonstrates this compensatory effec
t and provides a quantitative description of the results, Methods: Ventricu
lar myocytes from transgenic mice overexpressing the Na+/Ca2+ exchanger (TR
) and nontransgenic littermates (NON) were used. Cell shortening, cytoplasm
ic [Ca] (using indo-1 AM) and electrophysiological parameters were monitore
d. Results: TR myocytes displayed faster Ca2+ transients and twitches compa
red with NON myocytes. Superfusion with thapsigargin prolonged the time-cou
rse of Ca2+ transients of TR myocytes until these were equal to the ones me
asured in NON myocytes. The amount of SR Ca2+-ATPase (SERCA) inhibition nee
ded to obtain such transients was calculated as a function of V-max for the
Ca2+ flux via SERCA and found to be 28%. In TR myocytes V-max for the Ca2 flux via Na+/Ca2+ exchange was 240% of NON myocytes. When Ca2+ transients
in TR myocytes were slowed by thapsigargin to similar values to the ones re
corded in NON myocytes, SR Ca2+ content was also correspondingly reduced. C
onclusions: The results suggest that in pathophysiological conditions where
there is a reduction in SERCA function, overexpression of Na+/Ca2+ exchang
er can compensate and allow normal Ca2+ homeostasis to be maintained. In mo
use ventricular myocytes a 2.4-fold increase in Na+/Ca2+ exchange activity
compensates for a reduction in SERCA function by 28% so maintaining the dur
ation of the Ca2+ transient. (C) 2001 Elsevier Science B.V. All rights rese
rved.