INVESTIGADORES
ENNIS Irene Lucia
artículos
Título:
Silencing of NHE-1 blunts the slow force response to myocardial stretch
Autor/es:
PÉREZ NG; NOLLY MB; ROLDÁN MC; VILLA-ABRILLE MCM; CINGOLANI E; PORTIANSKY EL; ALVAREZ BV; ENNIS IL; CINGOLANI HE
Revista:
JOURNAL OF APPLIED PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Año: 2011
ISSN:
8750-7587
Resumen:
Myocardial stretch induces
a biphasic force response: A first abrupt increase followed by a slow force
response (SFR), believed to be the in vitro manifestation of the Anrep effect.
The SFR is due to an increase in Ca2+ transient of unclear mechanism.
We proposed that NHE-1 activation is a key
factor in determining the contractile response, but recent reports challenged
our findings. We aimed to specifically test the role of the NHE-1 in the SFR. To this purpose small hairpin interference RNA capable of mediating specific NHE-1
knockdown was incorporated into a lentiviral vector (l-shNHE1) and injected
into the left ventricular wall of Wistar rats. Injection of a lentiviral vector
expressing a non-silencing sequence (scramble) served as control. Myocardial
NHE-1 protein expression and function (the latter evaluated by the recovery of
pHi after an acidic load s and the SFR) were evaluated. Animals
transduced with l-shNHE1 showed reduced NHE-1 expression (45±8 % of controls, P<0.05) and the presence of the
lentivirus in the left ventricular myocardium, far from the site of injection,
was evidenced by confocal microscopy. These findings correlated with depressed basal
pHi recovery after acidosis [maxdpHi/dt
0.055±0.008 (scramble) vs. 0.009±0.004 (l-shNHE1) pHunits/min, P<0.05], leftward
shift of the relationship between JH+ (H+
efflux corrected by the intrinsic buffer capacity), and abolishment of SFR
[124±2 vs. 101±2 % of rapid phase, P<0.05] despite preserved ERK1/2
phosphorylation [247±12 (stretch) and 263±23 (stretch l-shNHE1) % of control,
P<0.05 vs. non-stretched control], well known NHE-1 activators. Our results
provide strong evidence to propose NHE-1 activation as key factor in
determining the SFR to stretch.