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M Aomine

Publications and source records attributed to M Aomine.

At least 55 records · Page 3Linked to original sources

Isotachophoretic evidence for energy-preservating effect of coenzyme Q10 on isolated guinea-pig cardiac muscle.

Effects of coenzyme Q10 (CoQ10) on hypoxia-induced changes in ATP, NAD and NADH levels were studied in the isolated atrial and ventricular muscles of guinea-pigs. Guinea-pigs were pretreated with CoQ10 (60 mg/kg/day, i.p.) or the solvent for 3 consecutive days before initiation of study. The concentrations of ATP, NAD and NADH were determined by isotachophoresis. The concentrations of ATP and NAD contained in the atrial or ventricular muscle decreased with increasing incubation time with hypoxic Tyrode's solution (pO2 not equal to 160 mmHG), but that of NADH increased. However, the ATP and NAD concentrations of atrial and ventricular muscles from CoQ10-pretreated animals tended to be higher than those from solvent-pretreated ones. Moreover, the increase in NADH concentration during hypoxia tended to be less in the CoQ10-pretreated preparation than in the solvent-pretreated one. These results suggest that the pretreatment with CoQ10 leads to the increase in CoQ10 content in mitochondria of heart muscle, thereby permitting the improvement of oxidative phosphorylation in the mitochondria during hypoxia.

Adenosine Triphosphate↗

Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

Effect of lysophosphatidylcholine (LPC) on the inward rectifier K channel of the isolated guinea pig ventricular cell was studied using patch clamp technique. In that LPC (100 microM) decreased the magnitude of the single channel conductance from 48 +/- 5 pS (mean and S.D., n = 5) to 12 +/- 9 pS (n = 8), this event may be the prime factor related to the alleged LPC-induced depolarization of cardiac tissues.

Animals↗

Nature of "residual fast channel" dependent action potentials and slow conduction in guinea pig ventricular muscle and its modification by isoproterenol.

The nature of "residual fast channel" dependent action potentials and conduction was studied in guinea pig ventricular papillary muscle in which the resting potential was reduced to 58 +/- 1 mV in high K+ (16.7 mM) Tyrode's solution, with or without isoproterenol (0.1 microM). In the absence of isoproterenol, the action potential had a slur on the upstroke and the maximum rate of rise (Vmax) was composed of 2 separable peaks: the early large (32 +/- 7 V/s, Vmax,fast) and the late small (10 +/- 2 V/s, Vmax,slow) ones. The conduction velocity ranged from 30 to 35 cm/s. The Vmax,fast was selectively depressed by l-verapamil (1 microgram/ml), indicating that the impulses were transmitted through incompletely inactivated ("residual") fast channels. Lidocaine (2 micrograms/ml) depressed Vmax,fast with reduction of conduction velocity to about 20 cm/s just before the conduction block. Isoproterenol quadrupled the Vmax,slow but decreased Vmax,fast. As a result, the Vmax,slow overrode the Vmax,fast without change in the conduction velocity. In the absence of isoproterenol, there was no rate-dependent change in the action potential duration and the effective refractory period among the rates of 0.1, 0.5, and 0.9 Hz. Isoproterenol produced rate-dependent shortening in action potential duration with rate-independent shortening of postexcitation refractoriness, thereby resulting in a significant shortening in the effective refractory period at faster rates (0.5 and 0.9 Hz). Results suggest that the "residual fast channel" could produce "slow conduction" and that the ionic channels (fast or slow) responsible for the slow conduction may alternate according to local concentrations of tissue catecholamines.

Action Potentials↗

Electrocardiogram and His bundle electrogram of Japanese monkeys (Macaca fuscata).

Electrocardiogram (ECG) was taken from Macaca fuscata in the supine position under secobarbital anesthesia. The ECGs were recorded in the leads of standard (I, II, III), augmented unipolar limb (aVR, aVL, aVF) and unipolar chest (V4R, V1, V2, V3, V4, V5, V6,). The ECG was similar to that of humans as well as the monkeys of other species in their general patterns and the voltage of each wave (P, Q, R, S, T), though the heart rate was considerably different. The direction of T wave was consistent with that of human ECG. The PR, QRS and QT intervals and the duration of P wave were in good agreement with those of monkeys of other species, and amounted to about 50% of those of human ECG. His bundle electrogram (HBE) was recorded with a tripolar electrode catheter inserted into the right ventricle via the femoral vein, and PA, AH, HV and PV intervals were measured. All of the values were also approximately 50% and PV intervals were measured. All of the values were also approximately 50% of those reported in human HBE. Such short time intervals observed in Macaca fuscata may be due to a smaller heart size of the monkey as compared to the human's. The measurements of ECG and HBE reported in the present study may be used as a normal reference in ECG and HBE of Macaca fuscata under anesthesia. The study suggests that the Macaca fuscata is useful as an animal model to investigate the repolarization process of human ECG.

Animals↗

Na, K-ATPase activity, ATP and Pi concentrations in various regions of monkey heart and their relation to post-overdrive hyperpolarization.

The relationship among Na, K-ATPase activity, ATP and inorganic phosphate (Pi) concentrations in functionally different regions of cardiac and skeletal muscles were studied in the Japanese monkey (Macaca fuscata). The activity of Na, K-ATPase was determined by the method of FIske and SubbaRow, and the concentrations of ATP and Pi, by isotachophoresis. The ATP concentrations in several regions of cardiac and skeletal muscles correlated positively with the Na, K-ATPase activities and Pi concentrations, whereas there was no significant correlation between the Na, K-ATPase activities and the Pi concentrations. Therefore, the ATP concentrations in functionally different regions of the tissues seemed to be a feasible measure of Pi concentrations and the Na, K-ATPase activities. The Na, K-ATPase activity was significantly higher in the epicardium than in the endocardium of the ventricle. The post-overdrive hyperpolarization was compared in these two tissues, using microelectrode methods. The hyperpolarization which followed overdrive stimulation (3.3-3.8 Hz) in the epicardium exceeded that in the endocardium, and was attributed to the difference in Na, K-ATPase activity. Our findings suggest that tissues with a higher Na, K-ATPase activity may have a more potent Na, K-pump activity, in association with higher tissue concentrations of ATP and Pi.

Adenosine Triphosphate↗

Effects of SG-75 (nicorandil) on electrical activity of canine cardiac Purkinje fibers: possible increase in potassium conductance.

The effects of various concentrations (1-1000 microM) of SG-75 nitrate or nicorandil) were investigated in action potentials of canine Purkinje fibers with microelectrodes. In normal fibers stimulated at the standard cycle length of 1500 msec, the drug (1-100 microM) produced dose-dependent shortening in action potential duration without changes in the resting potential, the maximum rate of rise of phase 0 and the slope of phase 4 depolarization. The drug-induced percentage of shortening in the action potential duration was more pronounced at lower rates of stimulation and lower external K+ concentrations, but the shortening was unchanged in lower external Na+ concentrations. Depolarizations produced by Ba++ (0.04 mM) and low K+ (less than or equal to 1.35 mM) solution were partially reversed by the drug, whereas there were no effects on the high K+ (5.4-24.7 mM)-induced depolarizations. Stretch-induced depolarization was also partially recovered in the presence of the drug. SG-75 shortened the duration of the slow response produced by isoproterenol (1 microM) in the presence of 24.7 mM K+, with little change in the maximum rate of rise. We concluded that SG-75 increases membrane K+ conductance in cardiac Purkinje fibers probably by modifying ix1 and iK1 channels without changing the slow inward currents and that the effects are not mediated by muscarinic receptors. The computed action potentials indicated that this view was reasonable.

Action Potentials↗

Electrophysiological and inotropic effects of Coenzyme Q10 on guinea pig ventricular muscle depolarized by potassium under hypoxia.

The electrophysiological and inotropic effects of Coenzyme Q10 (CoQ10) on isoproterenol or barium-induced slow responses in ventricular papillary muscle, depolarized by high K+ concentration (21.6 mM) under hypoxia (PO2 = 40 mmHg), were studied with microelectrode techniques. For the isoproterenol-induced slow response, application of CoQ10 (50 micrograms/ml), which was emulsified with the aid of a special solvent, increased the maximum rate of rise of action potentials (Vmax), an indicator of the slow inward current, by about 40%, with no consistent effect on the action potential duration and developed tension. Application of the solvent alone produced a significant decrease in both Vmax and developed tension. However, in these solvent-pretreated preparations, CoQ10 produced a significant (by about 50%) recovery in both Vmax and developed tension. The action potential duration was not changed by either the solvent alone or the application of CoQ10. The developed tension of the slow response consisted of early and late components. CoQ10 produced significantly more recovery in the late component than in the early one, suggesting that the recovery effect was due to increased slow inward Ca2+ current. CoQ10 did not reverse any parameter in the slow response induced by BaCl2 (0.2 mM). The results suggest that CoQ10 has significant but limited reversing effects on the hypoxia-induced deterioration of the slow response, and that the recovery is presumably due to increased availability of slow channels via increased production of ATP.

Action Potentials↗

Isotachophoretic analyses of metabolites of cardiac and skeletal muscles in four species.

We studied ATP and concentrations of other metabolites in cardiac and skeletal muscles from different species (frog, hamster, guinea-pig, and dog), using analytical capillary isotachophoresis. The method had several advantages for quantitative analysis of tissue metabolites: short separation time, high sensitivity, high resolution, and good reproducibility. It was also possible to detect a number of compounds simultaneously, including ATP, ADP, AMP, cyclic AMP, creatine phosphate (CP), inosine monophosphate, NAD, NADH, glucose-6-phosphate, pyruvate, and inorganic phosphate. Generally, the concentrations of high-energy phosphates (ATP and CP) in the cardiac muscle were significantly lower than those in the skeletal muscle, in all species tested, except for hamster where the concentration of CP in the skeletal muscle was comparable to that in the cardiac muscle. In mammals, ATP and CP concentrations were comparable in the atrium and ventricle while the concentration in the frog ventricle was significantly higher than that in the atrium. The data obtained by this isotachophoretic analysis were comparable to the data reported by the use of other conventional analytical methods. The significance and reliability of isotachophoresis in the determination of the various metabolites in the cardiac muscle were discussed.

Adenine Nucleotides↗

Surface layer ATP-related contraction in isolated, superfused canine ventricular papillary muscle: an isotachophoretic analysis.

The relationship among contractile tension, ATP content and concentration was examined in isolated, superfused ventricular papillary muscle under normoxic (Po2 not equal to 300 mmHg) and hypoxic (Po2 not equal to 100 mmHg) conditions, using capillary isotachophoresis. The muscle preparations were exposed to each condition for 30 min, and the contractile tension was recorded with a strain gauge. Immediately after the recordings, the preparations were homogenized and the metabolites (ATP, ADP, AMP, creatine phosphate, inosine monophosphate, NAD, NADH, glucose-6-phosphate, pyruvate, and inorganic phosphate) were extracted in 50% methanol-1.25 mM EDTA solution at -20 degrees C for 4 days. The supernatant of the extract was used for the isotachophoretic analysis. Hypoxia markedly depressed ATP content and concentration in the tissue. Under conditions of normoxia, but not hypoxia, the developed tension positively correlated with the ATP content and concentration. Under normoxic conditions, the tension tended to be proportional to the estimated surface area of the preparation, while in hypoxia it tended to be inversely proportional thereto. The ATP concentration appeared to be inversely proportional to the muscle weight, thereby suggesting that the outer layer of the preparation contains more ATP than the inner. In fact, an isotachophoretic analysis of the tissue revealed significantly higher ATP concentrations in the outer layer. Our findings indicate that there is a central anoxic core in the isolated canine papillary muscle superfused with oxygenated Tyrode solution and that surface layer ATP probably plays a pivotal role in the initiation of contraction.

Adenosine Triphosphate↗

The time-dependent and dose-dependent effects of the sulfhydryl blocker N-ethylmaleimide on the tonic tension in bullfrog atrium.

The kinetics of the inhibitory action by N-ethylmaleimide (NEM) on ICa-independent tonic tension in bullfrog atrial muscle was studied under voltage-clamped conditions, using the double sucrose gap method. The higher the concentration of NEM became, the larger was the rate of decrease of the tonic tension. In addition, the tension decreased with time of exposure to NEM. When the rate of the decrease of the tonic tension was plotted as a function of NEM concentration, the curve showed saturation kinetics of the Michaelis-Menten type with respect to NEM concentration, following the characteristics of a carrier-mediated process. Moreover, in the presence of excess Ca or half quantity of Na in Ringer solution, the curve showed sigmoidal kinetics. This probably indicates that the condition of either an excess of Ca or a reduction of Na in Ringer solution is apparently a cooperative effector of the inhibitory action of NEM, suggesting that the carrier protein responsible for the generation of tonic tension may be an allosteric protein. Finally, the relationship between ICa-independent tonic tension and the Na-Ca exchange mechanism which is supposed to be a powerful candidate for generating tension was discussed.

Animals↗

The action of N-ethylmaleimide on the membrane currents and contractile tension in the bullfrog atrium.

The effects of N-ethylmaleimide (NEM), a sulfhydryl blocking reagent, on the membrane currents, action potentials and contractile tension in bullfrog atrial muscle were studied by using the double sucrose gap technique. In concentrations of 10(-3) to 10(-4) M, NEM led to a transient enhancement of twitch contraction followed by a late inhibition, while 10(-2) M NEM merely produced an inhibitory effect. The positive inotropism was accompanied by a prolongation of action potential and the negative inotropism, by a depression of action potential. Under voltage clamp conditions, 10(-3) M NEM reduced the fast inward current and increased the steady state outward and background currents. The slow inward current and the inward Ca current in Na-free conditions were transiently increased by 10(-3) M NEM with an enhancement of contractile tension. In voltage-tension relationships, NEM-induced augmentation of tension appeared in depolarizing pulses of 60--70 mV. The results indicate that NEM increases transiently the Ca conductance of the cell membrane. Preincubation with L-cysteine blocked the production of positive inotropic effect by NEM, suggesting that the effects of NEM are due to the blockade of protein sulfhydryl group in the atrial muscle.

Action Potentials↗

Different effects of N-ethylmaleimide on the tension components of bullfrog atrium.

The effects of N-ethylmaleimide (NEM) on the tension components of bullfrog atrium were studied under voltage clamp conditions using the double sucrose gap technique. NEM at a dilution of 10(-3) M inhibited the ICa-independent tonic tension elicited by large and long depolarizing pulses (140 mV, 2 sec) time-dependently, whereas the drug produced an initial transient increase and a later decrease of the ICa-dependent phasic tension elicited by small and short depolarizing pulses (60 mV, 100 msec). The effect of NEM was facilitated when the atrial muscles were exposed to a solution having either a reduced Na or an increased Ca concentration. In the presence of Mn ions, 10(-3) M NEM did not evidently inhibit tonic tension, and it led to a slight transient increase in phasic tension. NEM at 10(-3) M, which is known to inhibit sarcolemmal Na, K-ATPase, enhanced both the phasic tension and the tonic tension in the presence of ouabain and when perfused with K-free solution. Even under these conditions (10(-3) M NEM caused an initial transient decrease of ICa-independent tonic tension. This suggests that NEM has a different action on the atrial muscle from those of cardiac glycosides such as ouabain.

Animals↗

Protective effect of histidine on iron (II)-induced hydroxyl radical generation in rat hearts.

We investigated the efficacy of histidine on iron (II)-induced hydroxyl radical (.OH) generation in extracellular fluid of the rat myocardium using a flexibly mounted microdialysis technique (O system). Rats were anesthetized and a microdialysis probe was implanted in the left ventricular, followed by infusion of sodium salicylate in Ringer's solution (0.5 nmol/microL/min) to detect the generation .OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Iron (II) clearly produced a concentration-dependent increase in .OH formation. A positive linear correlation between iron (II) and the formation of 2,3-DHBA (R2 = 0.987) was observed. However, histidine (25 mM) was infused through a microdialysis probe; iron (II) failed to increase the 2,3-DHBA formation obtained. To examine the effect of histidine on ischemia-reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the levels of 2,3-DHBA was observed in the heart dialysate. When corresponding experiments were performed with histidine (25 mM)-pretreated animals, histidine prevented the ischemia-reperfusion induced .OH generation trapped as 2,3-DHBA. These results indicate that histidine protects the myocardium against ischemia-reperfusion damage by .OH generation.

Animals↗