INHIBITION OF MITOCHONDRIAL H2S SYNTHESIS DEPRESSES HEART FUNCTION AND INCREASES SENSITIVITY OF MITOCHONDRIL PORE TO CALCIUM LOAD
А.Yu. Luchkova, Yu.V. Hoshovska, R.A. Fedichkina, N.А. Strutynska, V.F. Sagach
O.O. Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
The present study was aimed to investigate the effect of
О-carboxymethyl hydroxylamine (O-CMH) on heart function
in conditions of Ca2+ loads and mitochondrial permeability
transition pore (MPTP) opening in cardiac mitochondria. OCMH
(50 mg per kg) was dissolved in physiological solution
and injected intraperitoneally 30 min before the experiment.
Rat isolated hearts were Langendorf-perfused and subjected to
increased concentration of Ca2+ in perfusion solution ranged
from 1.7 to 12.5 mmoles/L. The heart function was assessed
by measuring the LVDP, dP/dt, the coronary flow, the heart
rate. The opening of MPTP was estimated by monitoring Ca2+
induced mitochondria swelling at 520 nm. The results showed
that pretreatment with O-CMH significantly depressed the
initial contractile activity of the isolated rat hearts and the
coronary flow. Further modeling of Ca2+ loads was accompanied
with lower increment of LVDP and dP/dt comparing to
control rats indicating decreased functional reserves and low
effectiveness of Ca2+ management in O-CMH pretreated rats.
Additionally, cardiac mitochondria in O-CMH group were
more sensitive to Ca2+ showing maximum swelling at 10-5
moles/L in the incubation medium vs 10-4 moles/L in control
group (p<0.05). Pre-incubation of cardiac mitochondria with
O-CMH in concentration of 10-5, 10-4 and 10-3 moles/L leaded
to increased Ca2+ induced swelling by 17.8, 20 and 44% respectively.
Thus, we have found that inhibition of mitochondrial
H2S synthesis pathway increase sensitivity of cardiac
mitochondria to Ca2+ that lead to mitochondrial swelling and
decreased ability of myocardium to manage Ca2+ homeostasis
by cardiomyocytes in conditions of Ca2+ load. This might
be proposed as the physiological role of H2S synthesized in
mitochondria by 3-MPST.
Key words: .
Hydrogen sulfide; calcium; MPTP; MPST; mitochondria; heart
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