INVESTIGADORES
PEREZ Nestor Gustavo
congresos y reuniones científicas
Título:
Inhibition of Carbonic Anhydrase Prevents the Na+/H+ Exchanger 1-dependent Slow Force Response to Rat Myocardial Stretch
Autor/es:
DÍAZ RG; VARGAS LA; SWENSON ER; PÉREZ NG; ÁLVAREZ BV
Lugar:
San Diego
Reunión:
Congreso; International Society for Heart Research (ISHR) XXI World Congress; 2013
Institución organizadora:
International Society for Heart Research (ISHR)
Resumen:
Myocardial stretch is an established signal
that leads to hypertrophy. Myocardial stretch induces a first immediate force
increase followed by a slow force response (SFR), which is a consequence of
increased Ca²+ transient that follows the NHE1 Na+/H+ exchanger activation.
Carbonic anhydrase II (CAII) binds to the
extreme C-terminus of NHE1 and regulates its transport activity. We aimed to
test the role of CAII bound to NHE1 in the SFR. The SFR and changes in
intracellular pH (pHi) were evaluated in rat papillary muscle bathed with
CO2/HCO3- buffer and stretched from 92% to 98% of the muscle maximal force
development length for 10 min, in the presence of the CA inhibitor
6-ethoxzolamide (ETZ, 100 ìM). SFR control
was120±3% (n=8) of the rapid initial phase and was fully blocked by ETZ, 99±4%
(n=6). The SFR corresponded with a maximal increase in pHi of 0.18±0.02 pH
units (n=4), and pHi changes were blocked by ETZ (0.04±0.04, n=6), monitored by
epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates.
CAII immunoprecipitated with anti-NHE1 antibody and the CAII immunoprecipitated
protein levels increased 58±9% (n=6) upon stretch of muscles, assessed by
immunoblots. The p90RSK kinase inhibitor SL0101-1 (10uM) blocked the SFR of heart muscles after stretch 102±2% (n=4), and reduced
the binding of CAII to NHE1, suggesting that the stretch-induced
phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction
constitutes a component of the SFR to heart muscle stretch which potentiates
NHE1-mediated H+ transport in the myocardium.