Effects of isoproterenol and suphan on the concentration of free calcium ions in isolated cardiomyocytes: a comparative study

Isoproterenol and suphan, two cardioactive drugs with different mechanisms of action, are studiedin vitro for their effects on calcium homeostasis in myocardial cells. Isoproterenol lowers the basal Ca²⁺ level in resting cardiomyocytes and potentiates its rise in these cells after their induction. Suphan stimulates reversible elevation of the diastolic Ca²⁺ concentration, causing increased calcium accumulation in the sarcoplasmic reticulum of cardiomyocytes. In anin vitro model of hypoxia, the Ca response to isoproterenol is significantly reduced, whereas that to dibutyryl cAMP is retained. The effect of suphan on the Ca²⁺ content of cardiomyocytes exposed to “chemical” hypoxia is 30–50% higher than its effect on the Ca²⁺ content of intact cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8 pp. 170–172, August, 1996     

Effect of human defensins on the cytoplasmic Ca2+ content in platelets

The effect of the total fraction of human defensins (HNP-1, HNP-2, and HNP-3) on the cytoplasmic Ca²⁺ content ([Ca²⁺]_i) in the platelets of healthy donors was studied. At concentrations of 0.1–40 μg/ml and an incubation time of 10 min defensins have no effect on [Ca²⁺]_i in platelets labeled with Fura-2AM. However, at higher concentrations (100 μg/ml) they increased platelet [Ca²⁺]_i. In addition, defensins (40 μg/ml) inhibited the Ca²⁺ increase in platelets induced by thrombin, adenosine diphosphate, and the lipopolysaccharide ofS. typhimurium endotoxin. The most pronounced inhibitory effect was observed in a suspension of thrombin-stimulated platelets. It is shown that the effect of human defensins on the functional activity of platelets is due to the alterations in the intracellular Ca²⁺. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 600–603, December, 1994     

A study of the mechanism of action of befol on Ca2+ metabolism in cardiomyocytes using a FURA-2 fluorescent probe

The dynamics of the Ca-response of cardiomyocytes is studied and the efficiency of befol, verapamil, and amiodarone is compared using various experimental models of stimulation of [Ca²⁺]_i. Befol (1–5 μM) is shown to inhibit the caffeine-and strophanthin G-induced rise of [Ca²⁺]_i. Unlike verapamil and amiodarone, befol exhibits no Ca-blocking activity in modeled K-depolarization. It is concluded that the cardiotropic effect of befol is mediated through its primary action on Na⁺/Ca²⁺ exchange in cardiomyocytes, while the cardioplegic effect of verapamil and amiodarone is due to their ability to block the slow Ca²⁺ inward current. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 288–291, March, 1996     

Opposite effect of adaptation to physical exercise on myocardium and skeletal muscle. Ca-transporting system of the sarcoplasmic reticulum and antioxidant defense enzymes

Adaptation to physical exercise was achieved via 60-min sessions of swimming at 32°C for 45 days, the duration of swimming being increased from 15 to 60 min during the first 14 days. Under these conditions, against the background of reduced catalase and superoxide dismutase activity the Ca-transporting system of the sarcoplasmic reticulum in the heart is shown to work more effectively: Ca²⁺ transport is characterized by a higher initial rate and is inactivated 1.5 times more slowly byin vitro-induced lipid peroxidation and not inhibited by high concentrations of free Ca²⁺. In the skeletal muscle, on the other hand, catalase and superoxide dismutase activity rise, but this does not improve the functioning of the Ca pump: the initial rate of Ca²⁺ transport drops, its resistance to autooxidation is not increased in comparison with the control, and the resistance of the Ca²⁺-transporting system to the inhibiting influence of free Ca²⁺ is lowered. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 6, pp. 623–628, June, 1996     

Na+/H+ countertransport and calcium exchange in peripheral blood cells of healthy subjects and patients with chronic heart failure

A comparative study is performed of Na⁺/H⁺ exchange and Ca²⁻ mobilization in erythrocytes and platelets of patients with stage I–II chronic heart failure caused by dilative cardiomyopathy and ischemic heart disease. A significant rise in the Na⁺/H⁺ exchange rate is found in the cells of chronic heart failure patients, which correlates with an elevated erythrocyte and platelet concentration of Ca²⁺ and an increased “calcium” response of platelets to inductors. The findings testify to a certain functional relationship between various cation-transporting cellular systems whose change in properties upon chronic heart failure can play an important pathogenic role. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 572–575, December, 1994     

Initiation of apoptosis in hepatocytes during prolonged arterial hypotension and postresuscitation period

An increase in activity of Ca²⁺, Mg²⁺-dependent endonucleases on the second hour of hypotension coincided with the presence of DNA fragments in agarose gel. A correlation was established between the duration of hypotension, Ca²⁺, Mg²⁺-dependent endonuclease activity, and intensity of nuclear DNA fragmention. Apopotosis of hepatocytes is triggered during ischemia and develops during reperfusion. Translated fromByulleten' Eksperimental'noi Biologii i Meditisiny, Vol. 125, No. 3, pp. 285–288, March, 1998     

Mechanism of action of the new cardiotonic suphan on calcium exchange in cardiomyocytes

Effects of suphan, a new cardiotonic agent containing succinyl tryptophan, on the entry of Ca²⁺ into rat cardiomyocytes, its intracellular compartmentalization, and its exit from these cells were evaluatedin vitro. It was found that the recorded sulfan-induced rise of intracellular calcium was due to Ca²⁺ entering the cell via L-type calcium channels, and that a reversible reduction of its concentration in the sarcoplasm occurred through its accumulation in the sarcoplasmic reticulum and was blocked by the specific Ca²⁺-ATPase inhibitor thapsigargin (10 μM). Suphan did not alter the activity of Na⁺/Ca²⁺ exchange in a concentration range of 5–150 μg/ml. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 57–59, July, 1996     

Effects of calcium and its antagonists on hemodynamics and respiration

Acute tests on cats under Nembutal anesthesia show that intravenous injection of Ca²⁺ causes pathological respiration of the apneustic type and slight rises in pulmonary and arterial pressures. The calcium channel blockers verapamil and nifedipine decrease the amplitude of respiratory movements, increase the respiration rate and pulmonary pulse pressure, and lower systemic pressure. The introduction of verapamil or nifedipine into the fourth ventricle of the brain does not alter respiration or hemodynamics, whereas the introduction of Ca²⁺ leads to irreversible respiratory standstill. Hemodynamic parameters decrease 2–3 min after the respiratory standstill. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8, pp. 138–143, August, 1996     

Adaptation to periodic hypoxia and a diet supplemented with polyunsaturated class ω-3 fatty acids enhance the resistance of Ca2+ transport in the myocardial sarcoplasmic reticulum to free-radical oxidation

The relationship between the level of accumulation of lipid peroxidation products and the status of the Ca²⁺-transporting system in the sarcoplasmic reticulum of the rat myocardium is studied against the background of two cardioprotective factors, namely adaptation to periodic hypoxia and a diet enriched in polyunsaturated fatty acids of the ω-3 class. It is shown that the diet leads to an increase of level of lipid peroxidation products by 1.8 times in the heart and by 19 times in the liver, whereas a adaptation has no effect on the level of lipid peroxidation products in either of these organs. At the same time, the combined action of both factors considerably enhances the resistance of the myocardial Ca²⁺-transporting system to free radical-induced oxidation. Inin vitro experiments it is shown that adaptation to periodic hypoxia results in a more than twofold deceleration of Ca²⁺ transport inhibition during the oxidation induction by the Fe²⁺/ascorbate system; the diet causes a 3.5-fold deceleration of such inhibition. The results show that the accumulation of a high level of lipid peroxidation products is not always followed by damage to the Ca²⁺-transporting system in the myocardial sarcoplasmic reticulum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 7, pp. 42–45, July, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Effect of vinpocetine on various types of high-threshold potassium currents in snail neurons

A high-threshold (−20 mV) K⁺ current was recorded from isolated edible snail neurons by a two-microelectrode voltage clamp technique. This current consisted of three components: fast-inactivating K⁺ currents (I_A), noninactivating K⁺ current (I_KD), and Ca²⁺-dependent K⁺ current (I_K(Ca)). Different cells had one to three components of K⁺ current. Vinpocetine increased I_A, moderately inhibited I_KD (by 30–50%) and strongly suppressed I_K(Ca) (by 60–90%). Inhibition of I_K(Ca) was not related to the effect of vinpocetine on the inward Ca²⁺ current. When K⁺ current consisted of all three components, the effect of vinpocetine on the ionic current amplitude was opposite at different potentials. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 408–411, October, 1998     

Effect of calcium channel blocker verapamil on DNA synthesis and activity of nucleolar organizer in cardiomyocytes of newborn albino rats

Fivefold administration of L-type Ca²⁺ channel blocker verapamil in a dose of 1.5 mg/kg to newborn rats increased the parameters of DNA-synthetic activity in the myocardium: labeling index and intensity increased 1.24-fold on average. Body weight decreased with simultaneous increase in the absolute and relative heart weight. Morphometric parameters of the nucleus and nucleoli were practically unaffected. Our findings suggest that the Ca²⁺ channel blocker verapamil administered at the early postnatal stages can modulate morphogenesis of the heart Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 658–660, June, 1999     

Ca-dependent ATPase activity and lipid peroxidation in the microsome fraction of renal medulla after thermal ischemia with and without α-tocopherol protection

Thermal ischemia of rat kidneys for 30 min induces lipid peroxidation with simultaneous activation of Ca-dependent ATPase in microsomes. In the presence of the channel-forming antibiotic alamethicin this activity decreases, indicating an increased passive permeability of the membrane vesicles for Ca²⁺ and ATP with a decrease in the true activity of the enzyme after ischemia. α-Tocopherol reduces the intensity of lipid peroxidation in the microsome fraction isolated from kidneys after thermal ischemia and protects ATPase activity in the presence and absence of alamethicin in the incubation medium. It is suggested that peroxidation of membrane phospholipids activated by thermal ischemia is one of the causes of decreased true activity of Ca-dependent ATPase and increased passive permeability of the kidney membranes for Ca²⁺ and ATP. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 289–291, September, 1997     

The effect of delta-sleep-inducing peptide on the Ca-transporting system of the sarcoplasmic reticulum and activity of the myocardial antioxidant enzymes

It is demonstrated that immobilization stress against the background of lowered catalase activity impairs the function of the sarcoplasmic reticulum Ca pump, particularly at high Ca²⁺ levels. the membranes of intracellular Ca²⁺ depots are destroyed much more rapidly than in the control, which results in Ca²⁺ release. Administration of delta sleep-inducing peptide to control animals results in a 30% increase in catalase activity for an unchanged level of superoxide dismusase and markedly improves the function of the Ca-transporting system at elevated levels of free Ca²⁺. A long-term stress after administration of the peptide not only causes no damage to the Ca-transporting system but actually increases its efficiency (compared with the control) at a high catalase level. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 248–251, March, 1996 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Effects of some steroid hormones on Ca2+ transport and oxidative metabolism of isolated mitochondria

Effects of prednisolone, estradiol, and testosterone on the transport of Ca²⁺ and the respiration induced by it in the heart and liver mitochondria of rats were studied. Prednisolone and testosterone were found to reduce the Ca-accumulating capacity of the mitochondria, the rates of ion entry and exit, and the rate of Ca²⁺-induced respiration. Estradiol, while inhibiting Ca²⁺ transport across mitochondrial membrane, did not influence the respiration in the phase of Ca²⁺ absorption, but accelerated it in the phase of ion exit. These data suggest that due to their lipophilic properties, the steroids become incorporated in the mitochondrial membrane, thereby changing its viscosity and permeability and limiting the mobility of transmitter proteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 616–618, December, 1994     

Effects of the nootropics piracetam and GVS-111 on voltage-dependent ion channels of neuronal membranes

The effect of two nootropics, piracetam and N-phenylacetyl-L-prolyglycine ethyl ester (GVS-111), is studied by measuring high-threshold K⁺ and Ca²⁺ currents in isolated snail neurons using a two-microelectrode patch-clamp technique. Piracetam and GVS-111 are shown to reduce the amplitude of both the K⁺ and the Ca²⁺ (to a lesser extent) current. The threshold concentrations for GVS-111 and piracetam are 10⁻⁹-10⁻⁸ M and 1–5×10⁻⁴ M, respectively. It is assumed that the antiamnestic effect of the nootropics is partially mediated by a blockade of ion channels of the neuronal membrane. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 151–155, February, 1996 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

The calcium channel antagonist diltiazem effectively blocks two types of potassium channels in the neuronal membranes

Effect of the Ca²⁺-channel antagonist diltiazem on potential-operated Ca²⁺ and K⁺ currents was studied on isolated edible snail neurons by a two-microelectrode patch-clamp technique. Diltiazem in a concentration of 0.1 mM inhibits Ca²⁺ current, high-threshold Ca²⁺-dependent K⁺ current, and Ca²⁺-independent K⁺ current and has no effect on low-threshold K⁺ current and leakage current. It is suggested that therapeutic effect of diltiazem is mediated through blockade of Ca²⁺ and K⁺ channels. Tranlated fromByulleten' Eksperimental'noi biologii i Meditsiny, Vol. 124, No. 9, pp. 271–274. September, 1997     

45Ca exchange in rat cortex slices in conditions of long-term potentiation

Existing data on the role of Ca²⁺ ions in the development of long-term potentiation were used as a basis for studying changes in different Ca²⁺ compartments in cells in living rat olfactory cortex slices during potentiation. The kinetics of⁴⁵Ca²⁺ exchange were studied at 5, 15, and 30 min of potentiation. During the induction phase (1–5 min) of long-term potentiation, the fraction of tightly-bound intracellular Ca²⁺ decreased. There were no changes in the content of Ca²⁺ ions in other fractions at this stage. During maintenance of potentiation, which lasted 15–25 min, Ca²⁺ levels in the extracellular and intracellular compartments did not differ from controls. At 30 min, during extinction of long-term potentiation, there was a significant redistribution of Ca²⁺ in cells: the levels of free and loosely-bound Ca increased, as did extracellular Ca²⁺. Laboratory of Functional Neurochemistry, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, St. Petersburg 199034, Russia. Translated from Rossiiki Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 7, pp. 45–49, July, 1997.     

Effect of benzodiazepines on synaptosomal Ca2+ transport in mice with different phenotype of emotional stress reactions

The effects of 5 benzodiazepines on basal and K⁺-induced Ca²⁺ concentration in synaptoneurosomes from intact and stressed C57B1/6 and BALB/c mice were studiedin vitro. Membrane depolarization induced by low KCl concentrations produced different effects on Ca²⁺ accumulation by synaptoneurosomes from two mouse strains. Benzodiazepines appliedin vitro exerted no effects on Ca²⁺ influx. In synaptoneurosomes from both C57B1/6 and BALB/c mice exposed to emotional stress diazepam in a dose of 5 mg/kg reduced the basal and K⁺-induced Ca²⁺ accumulation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 3, pp. 304–305, March, 2000     

Effect of emergent and long-term adaptation to physical strength on the resistance of Ca-transporting system of myocardial sarcoplasmic reticulum

Experiments were carried out on rats adapted to physical exercise (on the next day after completion of 4, 11, 15, and 30 swimming sessions). Catalase and superoxide dismutase activities were similar in all rats. The resistance of Ca transport into sarcoplasmic reticulum to high Ca²⁺ concentrations and autooxidaton increased starting from 4 swimming sessions, and to thermal inactivation from 11 sessions; the maximum resistance was attained after 15 sessions 1.5- to 2-fold surpassing the initial level. Maximum initial rate of Ca²⁺-transport (155% of the control) was observed after 30 swimming sessions. In acute physical strength and at the initial stages of adaptation (4 swimming sessions) functional properties of myocardial Ca-transporting system were preserved under optimal conditions, but can be readily disturbed by adverse factors. Translatedfrom Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 1, pp. 40–44, January, 1998 Original     

Effect of ricin and its B-subunit on calcium responses in human lymphocytes

The effect of ricin and its B-subunit on cytoplasmic Ca²⁺ concentration in human lymphocytes was studied using a fluorescence probe. Both agents dose-dependently increased cytosolic free Ca²⁺ by stimulating its release from of thapsigargin-sensitive store. It is suggested that this effect is associated with the increase in cytosolic content of inositol-1,4,5-trisphosphate. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 3, pp. 274–276, March, 2000