Effects of purified endogenous inhibitor of the Na+/Ca2+ exchanger on ouabain-induced arrhythmias in the atria and ventricle strips of guinea pig.

Previous studies demonstrated that the purified endogenous inhibitor (NCX(IF)) of the cardiac Na(+)/Ca(2+) exchanger (NCX1) has the capacity to modulate cardiac muscle contractility. Here, we tested the effects of purified NCX(IF) on arrhythmias induced by ouabain in the atria and ventricle strips of guinea pig. For the sake of comparison NCX(IF) was compared to lidocaine and KB-R7943.

Purified endogenous inhibitor of the Na/Ca exchanger can enhance the cardiomyocytes contractility and calcium transients.

Previous studies have shown that the newly found endogenous inhibitor (NCX(IF)) of the cardiac Na/Ca exchanger (NCX1) is capable of regulating the muscle strip's contractility and relaxation. Here, the effects of purified NCX(IF) were tested on single cell shortening-lengthening (by using the IR CCD camera coupled with the two-edge video-detector) and [Ca]i-transients (by monitoring the changes in fluo-3 fluorescence). A perfusion of isolated cardiomyocytes (paced at 0.

Advanced procedures for separation and analysis of low molecular weight inhibitor (NCXIF) of the cardiac sodium-calcium exchanger.

A low molecular weight inhibitor (NCX(IF)) of the cardiac Na/Ca exchanger, isolated from the calf ventricle tissue, is capable of regulating the muscle strip's contractility and relaxation without involving the beta-activation pathway. The structural analysis of NCX(IF) requires highly purified preparations that fulfill the demanding requirements for mass spectra and NMR analyses. No such preparation is yet available.

The low molecular weight inhibitor of NCX1 interacts with a cytosolic domain that differs from the ion-transport site of the Na/Ca exchanger.

The endogenous inhibitory factor (NCX(IF)) of the cardiac Na/Ca exchanger (NCX1) is a low molecular weight substance, which has a strong capacity to modulate the ventricle muscle contractility. Previously, we have shown that NCX(IF) can completely inhibit either the forward (Na(i)-dependent Ca-uptake) or reverse (Na(o)-dependent Ca-release) mode of Na/Ca exchange as well as its partial reaction, the Ca/Ca exchange. Although the preliminary studies have shown that NCX(IF) can rapidly (within few milliseconds) interact with a putative inhibitory site of the Na/Ca exchanger protein (or within its vicinity), it was not clear whether the NCX(IF) can directly interact with the ion transport sites of the exchanger protein or the interaction site of NCX(IF) is distinct from the ion-binding/transport site of NCX1.

Inotropic and lusitropic effects induced by the inhibitory factor of the Na/Ca exchanger are not mediated by the beta-adrenergic activation.

Recently, an endogenous inhibitory factor (NCXIF) of the cardiac Na/Ca exchanger (NCX1) has been isolated, purified, and preliminary characterized. Here, we demonstrate that low doses of NCXIF (10(-7)10(-8) M) induce strong inotropic effects in the guinea and rat ventricle strips, while having no detectable effects in the atria even at 10(-5) M. The inotropic effects of NCXIF are species-specific; the rat ventricle muscle is 20 to 50 times more sensitive to varying doses of NCXIF than the guinea pig.

The endogenous inhibitor of NCX1 does not resemble the properties of digitalis compound.

In our previous study, we ware successful in isolation and purification of an endogenous inhibitor of the Na/Ca exchanger (NCX1) from the calf ventricle extracts. The purified factor has characterized to have strong positive inotropic effect on isometric contractions of isolated ventricle strips of guinea pig. A possibility is that besides the NCX1 the endogenous factor may also interact with other ion-transport systems (e.