A Comparative Study on the Effects of the Lysine Reagent Pyridoxal 5-Phosphate and Some Thiol Reagents in Opening the Tl-Induced Mitochondrial Permeability Transition Pore.

Lysine residues are essential in regulating enzymatic activity and the spatial structure maintenance of mitochondrial proteins and functional complexes. The most important parts of the mitochondrial permeability transition pore are F1F0 ATPase, the adenine nucleotide translocase (ANT), and the inorganic phosphate cotransporter. The ANT conformation play a significant role in the Tl-induced MPTP opening in the inner membrane of calcium-loaded rat liver mitochondria.

The Joint Influence of Tl and Thiol-Modifying Agents on Rat Liver Mitochondrial Parameters In Vitro.

Recent data have shown that the mitochondrial permeability transition pore (MPTP) is the complex of the Ca-modified adenine nucleotide translocase (ANT) and the Ca-modified ATP synthase. We found in a previous study that ANT conformational changes may be involved in Tl-induced MPTP opening in the inner membrane of Ca-loaded rat liver mitochondria. In this study, the effects of thiol-modifying agents (eosin-5-maleimide (EMA), fluorescein isothiocyanate (FITC), Cu(o-phenanthroline) (Cu(OP)), and embelin (Emb)), and MPTP inhibitors (ADP, cyclosporine A (CsA), n-ethylmaleimide (NEM), and trifluoperazine (TFP)) on MPTP opening were tested simultaneously with increases in swelling, membrane potential (ΔΨ) decline, decreases in state 3, 4, and 3U (2,4-dinitrophenol-uncoupled) respiration, and changes in the inner membrane free thiol group content.

Mitochondrial mechanisms by which gasotransmitters (HS, NO and CO) protect cardiovascular system against hypoxia.

Over past few years, there has been a dramatic increase in studying physiological mechanisms of the activity of various signaling low-molecular molecules that directly or indirectly initiate adaptive changes in the cardiovascular system cells (CVSC) to hypoxia. These molecules include biologically active endogenous gases or gasotransmitters (HS, NO and CO) that influence on many cellular processes, including mitochondrial biogenesis, oxidative phosphorylation, K/Ca exchange, contractility of cardiomyocytes (CM) and vascular smooth muscle cells (VSMC) under conditions of oxygen deficiency. The present review focuses on the mechanistic role of the gasotransmitters (NO, HS, CO) in cardioprotection.

Compact generators of high-power fast-rising pulses with closing switches in the form of reversely switched dynistors.

This paper presents the results of a study of reversely switched dynistors (RSDs) with an operating voltage of 2.3 kV and a structure diameter of 12 mm in an unconventional mode, when they commutate current pulses with very short durations (a few microseconds). In this mode, we studied the dependence of the switching energy loss on the amount of charge that passes through the RSDs during the flow of the control current, which is reversed with respect to the main current.

High voltage microsecond pulse generators with highly effective energy recuperation in cases of sharp changes in load impedance.

An experimental generator of microsecond pulses with an output current amplitude of ∼1 kA and an output voltage amplitude of ∼1 kV was developed. The generator is able to operate on a load whose electrical resistance changes significantly during operation. Under these conditions, the generator ensures high stability of output pulse energy and effectively uses energy that is reflected from the load.

Effects of Tl on the inner membrane thiol groups, respiration, and swelling in succinate-energized rat liver mitochondria were modified by thiol reagents.

The effects of both Tl and thiol reagents were studied on the content of the inner membrane free SH-groups, detected with Ellman reagent, and the inner membrane potential as well as swelling and respiration of succinate-energized rat liver mitochondria in medium containing TlNO and KNO. These effects resulted in a rise in swelling and a decrease in the content, the potential, and mitochondrial respiration in 3 and 2,4-dinitrophenol-uncoupled states. A maximal effect was seen when phenylarsine oxide reacting with thiol groups recessed into the hydrophobic regions of the membrane.

Silicon dynistors with subnanosecond switching times.

High-voltage silicon dynistors, which are turned on by means of initiating a shock ionization process in silicon, have unique capabilities with regard to switching of current pulses of a nanosecond duration. This paper describes the design of shock-ionized dynistors (SIDs) optimized to reduce the energy loss during switching. The use of these SIDs allows for a twofold reduction in the triggering generator's power consumption.

[Features of autonomic regulation of the cardiovascular system in human late ontogenesis.].

Using the method of arterial piezopulsometry, statistical and spectral analyzes of variable parameters (VmaxPP and TNN) of pulse waves of blood pressure in patients aged 18 to 85 years were performed. The individual characteristics of the autonomous (vegetative and neuroendocrine) regulation of the muscular effectors (ME) of the cardiovascular system (CVS) in an elderly man (75 years old) and a young woman (20 years old) were estimated with high accuracy. These data, as well as the results of a comparative study of patients of different ages, made it possible to identify a certain pattern of directed change in the sympathoadrenal regulation of ME CVS in human ontogenesis.

Effects of Pinacidil and Calcium on Succinate-Energized Rat Heart Mitochondria in the Presence of Rotenone.

The effect of pinacidil was studied on calcium-loaded rat heart mitochondria (RHM) in the presence of succinate and rotenone. In experiments with pinacidil, the swelling of these mitochondria increased in media with NHNO or K-acetate, but the inner membrane potential (ΔΨ) and the respiration in 3 or 2,4-dinitrophenol-stimulated states of these organelles decreased due to the opening of the mitochondrial permeability transition pore (MPTP) in their inner membrane. These effects were inhibited by cyclosporin A and ADP.

Mersalyl prevents the Tl-induced permeability transition pore opening in the inner membrane of Ca-loaded rat liver mitochondria.

It was earlier shown that the calcium load of rat liver mitochondria in medium containing TlNO and KNO resulted in the Tl-induced mitochondrial permeability transition pore (MPTP) opening in the inner membrane. This opening was accompanied by an increase in swelling and membrane potential dissipation and a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration. This respiratory decrease was markedly leveled by mersalyl (MSL), the phosphate symporter (PiC) inhibitor which poorly stimulated the calcium-induced swelling, but further increased the potential dissipation.

ATP-consuming processes in hepatocytes of river lamprey Lampetra fluviatilis on the course of prespawning starvation.

The work was performed to establish which of the major ATP-consuming processes is the most important for surviving of hepatocytes of female lampreys on the course of prespawning starvation. The requirements of protein synthesis and Na(+)-K(+)-ATPase for ATP in the cells were monitored by the changes in mitochondrial membrane potential (MMP) in the presence of corresponding inhibitors from the peak of metabolic depression (January-February) to the time of recovery from it (March-April) and spawning (May). Integrity of lamprey liver cells was estimated by catalytic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood plasma.

Data supporting the involvement of the adenine nucleotide translocase conformation in opening the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

There we made available information about the effects of the adenine nucleotide translocase (ANT) 'c' conformation fixers (phenylarsine oxide (PAO), tert-butylhydroperoxide (tBHP), and carboxyatractyloside) as well as thiol reagent (4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)) on isolated rat liver mitochondria. We observed a decrease in A540 (mitochondrial swelling) and respiratory control rates (RCRADP [state 3/state 4] and RCRDNP [2,4-dinitrophenol-uncoupled state/basal state or state 4]), as well as an increase in Ca(2+)-induced safranin fluorescence (F485/590, arbitrary units), showed a dissipation in the inner membrane potential (ΔΨmito), in experiments with energized rat liver mitochondria, injected into the buffer containing 25-75 mM TlNO3, 125 mM KNO3, and 100 µM Ca(2+). The fixers and DIDS, in comparison to Ca(2+) alone, greatly increased A540 decline and the rate of Ca(2+)-induced ΔΨmito dissipation.

[COMPARATIVE STUDY OF Y³⁺ EFFECT ON CALCIUM-DEPENDENT PROCESSES IN FROG CARDIAC MUSCLE AND IN MITOCHONDRIA OF RAT CARDIOMYOCYTES].

Inotropic effects of yttrium acetate (Y³⁺) on contractions of myocardium preparations of the frog Ra- na ridibunda as well as on respiration and the inner membrane potential (Δψmito) of isolated rat heart mi- tochondria were studied. It was found that 2 mM yttrium in Ringer solution significantly reduced the am- plitude of myocardium contractions evoked by electric stimulation and increased the half-relaxation time (n = 5). In experiments with Ca²⁺, Y³⁺ decreased Ca²⁺-dependent oxygen consumption rate of rat heart mitochondria, energized by glutamate and malate, impeded the reduction in respiration of these mito- chondria in state 3 or uncoupled by 2,4-dinitrophenol, and inhibited Ca²⁺-induced decrease in their inner membrane potential.

To involvement the conformation of the adenine nucleotide translocase in opening the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

The conformation of adenine nucleotide translocase (ANT) has a profound impact in opening the mitochondrial permeability transition pore (MPTP) in the inner membrane. Fixing the ANT in 'c' conformation by phenylarsine oxide (PAO), tert-butylhydroperoxide (tBHP), and carboxyatractyloside as well as the interaction of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) with mitochondrial thiols markedly attenuated the ability of ADP to inhibit the MPTP opening. We earlier found (Korotkov and Saris, 2011) that calcium load of rat liver mitochondria in medium containing TlNO3 and KNO3 stimulated the Tl(+)-induced MPTP opening in the inner mitochondrial membrane.

[AGED CARDIOHEMODYNAMICS COMPLICATED BY STROKE].

A new method of arterial piezopulsometry allowed a 12-year study of the peculiarities of age-related changes in cardiac hemodynamic indices in an aged man after ischemic stroke. The ob-tained results enable use of these indicators as prognostic criteria of an individual organism's re-sistance to acceleration factors of aging, as well as its resistance to the development of the cardi-ovascular pathology caused by the stroke. Simultaneous dual registration of piezopulsograms al-lowed establishing a significant increase of the augmentation index of pulse pressure (AIxPP) and the velocity of the pulse wave of blood pressure propagation through the radial artery (Var) in a paralyzed right arm, compared to the left hand control (p < 0,05).

Diamide accelerates opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

Opening of the mitochondrial permeability transition pore (MPTP) in the inner membrane is due to matrix Ca(2+) overload and matrix glutathione loss. Fixing the 'm' conformation of the adenine nucleotide translocase (ANT) by ADP or N-ethylmaleimide (NEM) inhibits opening of the MPTP. Oxidants (diamide or tert-butylhydroperoxide (tBHP)) fix the ANT in 'c' conformation, and the ability of ADP to inhibit the MPTP is thus attenuated.

[MECHANISMS OF THE EFFECT OF Li+ ON MYOCARDIUM OF VERTEBRATES].

The effect of Li+ on the frog Rana temporaria myocardium and its influence on the ion transport in the rat heart mitochondria (RHM) were studied. Li+ added to the normal Ringer solution (Li(+)-R) was found to attenuate myocardial tension, decrease the maximal rate of tension development and its half-relaxation time. Comparison of the cardiac muscle contraction parameters in the Li(+)-R with the effect of the voltage-gated Ca(2+)-channels (Cav1.

Tl+ induces the permeability transition pore in Ca2+-loaded rat liver mitochondria energized by glutamate and malate.

It is known that Ca2+ and heavy metals more actively induce MPTP opening in mitochondria, energized by the I complex substrates. Thus, a rise in a Tl+-induced MPTP was proposed in experiments on isolated rat liver mitochondria energized by the complex I substrate (glutamate and malate). Expose of the mitochondria to Ca2+ into a medium containing TlNO3, glutamate, and malate as well as sucrose or KNO3 resulted in a decrease in state 3, state 4, or DNP-stimulated respiration as well as an increase of both mitochondrial swelling and ΔΨmito dissipation.

Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+) activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al.

[Action of yttrium on calcium-dependent processes in myocardium of vertebrates].

This work deals with study, of effect of yttrium acetate (Y3+) on myocardium of the frog Rana redibunda and of its action on the ion transport across the inner membrane of the rat heart mitochondria. It was found that Y3+ decreased strength of heart contractions and facilitated transport of ions in rat heart mitochondria stimulated by 10 mM glutamate and 2 mM malate. In the presence of Y3+, the energy-dependent transport of Ca2+ in mitochondria was inhibited; this was manifested as a decrease of their swelling in the medium containing 125 mM NH4NO3 and Ca2+ or 25 mM potassium acetate, 100 mM sucrose and Ca2+.

[Inotropic effect of a new probiotic product on myocardial contractility. Comparison with diazoxide].

The inotropic effect of a new probiotic product on myocardial contractility of the frog Rana ridibunda and the effect of probiotic product on the rat cardiac mitochondria swelling were studied. In both cases, the comparison with known cardioprotector diazoxide was done. Probiotic product and diazoxide were shown to cause a dual effect on the maximum force induced by the muscle sample during spontaneous atrial contraction.

Y3+, La3+, and some bivalent metals inhibited the opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria.

We showed earlier that diminution of 2,4-dinitrophenol (DNP)-stimulated respiration and increase of both mitochondrial swelling and electrochemical potential (ΔΨmito) dissipation in medium containing TlNO3 and KNO3 were caused by opening of Tl(+)-induced mitochondrial permeability transition pore (MPTP) in the inner membrane of Ca(2+)-loaded rat liver mitochondria. The MPTP opening was studied in the presence of bivalent metal ions (Sr(2+), Ba(2+), Mn(2+), Co(2+) and Ni(2+)), trivalent metal ions (Y(3+) and La(3+)), and ruthenium red. We found that these metal ions (except Ba(2+) and Co(2+)) as well as ruthenium red inhibited to the MPTP opening that manifested in preventing both diminution of the DNP-stimulated respiration and increase of the swelling and of the ΔΨmito dissipation in medium containing TlNO3, KNO3, and Ca(2+).

On the mechanism(s) of membrane permeability transition in liver mitochondria of lamprey, Lampetra fluviatilis L.: insights from cadmium.

Previously we have shown that opening of the mitochondrial permeability transition pore in its low conductance state is the case in hepatocytes of the Baltic lamprey (Lampetra fluviatilis L.) during reversible metabolic depression taking place in the period of its prespawning migration when the exogenous feeding is switched off. The depression is observed in the last year of the lamprey life cycle and is conditioned by reversible mitochondrial dysfunction (mitochondrial uncoupling in winter and coupling in spring).

[Action of La3+ on the systems providing contractility of vertebrate myocardium].

The inotropic action of La3+ on frog myocardium was studied with taking into account of its effect on mitochondria of cardiomyocytes (CM). It has been established that in the range of studied concentrations (0.2-6 mM), La3+ decreases dose-dependently the strength of cardiac contractions (by 3.