Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and “ischemic” conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) (p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT (p = 0.001), whereas VT/VF incidence was associated with baseline ATs (p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation (p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.

No abstract

Effects of infrared (IR) radiation generated by a low-power Co2-laser on sensory neurons of chick embryos were investigated by organotypic culture method. Low-power IR radiation firstly results in marked neurite suppressing action, probably induced by activation of Na+,K+-ATPase signal-transducing function. A further increase in energy of radiation leads to stimulation of neurite growth. We suggest that this effect is triggered by activation of Na+,K+-ATPase pumping function. Involvement of Na+,K+-ATPase in the control of the transduction process was proved by results obtained after application of ouabain at very low concentrations. Physiological significance of low-power IR radiation and effects of ouabain at nanomolar level was investigated in behavioral experiments (formalin test). It is shown that inflammatory pain induced by injection of formalin is relieved both due to ouabain action and after IR irradiation.

No abstract

We studied the effects of ouabain, norepinephrine, and acetylcholine on the growth of heart tissue explants from 10-12-old chicken embryos in an organotypic culture. Ouabain, norepinephrine, and acetylcholine stimulated the growth of explants. Our results suggest that trophic function of acetylcholine and norepinephrine is associated with regulation of Na,K-ATPase activity as a signal transducer.

We studied the effects of acetylcholine and norepinephrine on the growth of neurites in organotypic culture of 10-12-day-old chick embryo sensory neurons. Acetylcholine (10(-8) M) and norepinephrine (10(-13) M) stimulated the growth on sensory neuron neurites. Experiments with combined application of acetylcholine and norepinephrine against the background of ouabain showed that the nonspecific action of the test neurotransmitters is related to modulation of Na/K-ATPase activity.

Complete conformational analysis of 1 : 1 calcium(II) chelates with ouabagenin was performed ab initio. Analysis of the effect of complex formation on the steric and electronic structures revealed that ouabagenin molecule is capable of coordinating Ca 2+ ion in three different modes. The lack of rhamnose fragment in the ouabagenin molecule, in contrast to ouabain, sharply reduces its physiological activity related to its ability to bind at transducer Na + /K + -ATPase site.Cardiotonic steroids constitute a class of compounds capable of selectively binding to extracellular surface of Na + /K + -ATPase; the latter is an enzyme which utilizes the energy of ATP hydrolysis for active transport of Na + and K + ions through cell membranes [1][2][3][4]. This class of compounds includes both glycosides (such as ouabain and digoxin) and aglycones (ouabagenin, strophadogenin, adonitoxigenin). Clinical applications of cardiotonic steroids is based on their ability to exert a positive inotropic effect on myocard via partial inhibition of Na + /K + -ATPase in myocard cells [4]. The results of recent studies have shown that Na + /K + -ATPase can act as signal transducer which controls nociceptive information transmission in sensor neurons of warm-blooded animals [5], as well as cell growth and proliferation in various tissues [6][7][8][9][10][11][12][13][14].Using the organotypic tissue culture technique, it was shown that ouabain in nanomolar concentration range (which is comparable with the endogenous ouabain level) is capable of modulating transducer function of Na + /K + -ATPase in nervous and cardiac tissues [11][12][13]15]. Ligand-receptor interaction of ouabain molecule with some amino acid sequence of the enzyme is likely to involve formation of the ternary complex ouabain-Ca 2+ -Na + /K + -ATPase [15]. Nonempirical quantum-chemical calculations showed that ouabain molecule is theoretically capable of chelating Ca 2+ ion, and six possible conformations of the complexes thus formed were found [15]. In continuation of our studies on the ability of cardiotonic steroids to modulate transducer activity of Na + /K + -ATPase, we examined the effect of ouabagenin [1β,3β,5β,11α,-14β,19β-hexahydroxycard-20(22)-enolide] on the growth of neurites of sensor ganglia and cardiac tissue explants in 10-12-day chicken embryos using the organotypic tissue culture technique. Ouabagenin at

We studied the role of cardiac glycosides in the regulation of the growth of retinal tissue explants from 10-12-day-old chicken embryos in organotypic culture. The studied compounds produced a dose-dependent effect on cell proliferation in retinal tissue explants. Ouabain (10(-13)M), strophanthin K (10(-13)M) and digoxin (10(-11)M) significantly stimulated explant growth. It was hypothesized that the physiological role of endogenous ouabain is associated with regulation of tissue modeling.