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Mechanisms of action of hypersodium mediumon contractile activity of isolated rat heart
V. V. Alabovsky, E. J. Cragoe, A. A. Winokurov
Department of Biochemistry Voronezh State Medical Academy, Russia
Abstract
V. V. Alabovsky, E. J. Cragoe, A. A. Winokurov
MECHANISMS OF ACTION OF HYPERSODIUM MEDIUM
ON CONTRACTILE ACTIVITY OF ISOLATED RAT HEART
Despite the high efficiency of elevated concentrations of sodium ions during myocardial
ischemia and calcium paradox, the molecular mechanism of action of hypersodium
media on heart contractions remains unknown. The purpose of the investigation was
to study mechanisms by which raised concentrations of sodium ions alter cardiac
contractility. Subsequent to initially developed reduced pressure in the left ventricle,
elevated concentrations of sodium ions (200 mM instead of 140 mM NaCl, 3 mM
KCl) produced an increased force of contractions of about 50%. The first stage of
decrease in developed pressure did not relate to elevated tonicity of extracellular
ionic millieu because lithium chloride (60 mM) did not produce the same effect. This
action of elevated concentrations of sodium ions has been shown to be independent of
blockers of ion-transporting systems (caffeine, verapamile, ethmozine, HMA or
lidocaine). Raising the contractions by elevating the concentration of sodium ions
(second stage) has been shown to be susceptible to sodium channel blockers (6-IA,benzamil, of phenamil) and to cafeine. Decreasing of potassium concentration (from
3 mM to 1—2 mM amplified, and increasing of K+ level (from 3 mM to 6 mM)
attenuated the positive inotropic action of the elevated concentration of sodium
ions. The positive inotropic effect due to elevated concentrations of sodium ions
remains even after heart arrest by high concentrations of verapamile (2 mcM). Lithium
chloride (60 mM) failed to elevate left ventricle developed pressure which was raised
by elevated concentrations of sodium ions. These data suggest that the elevated
concentration of sodium ions could effect Na+/Ca2+ exchange and provoke Ca2+ release
from sarcoplasmic reticulum by changing the sodium gradient and resulting in Ca2+
entry via Na+/Ca2+ exchange. These observations are consistent with the hypothesis
of Leblanc N., Hume J.R. (1990) regarding sodium-induced calcium ion release from
sarcoplasmic reticulum.
Department of Biochemistry Voronezh State Medical Academy, Russia
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