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J Y Su

Publications and source records attributed to J Y Su.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effects of ryanodine on skinned myocardial fibers of the rabbit.

Skinned fiber bundles from papillary muscle of rabbits were used to study the effects of ryanodine (1) on direct Ca2+ activation of the contractile proteins, and (2) on direct Ca2+ uptake and release from the sarcoplasmic reticulum (SR). Caffeine (25 mM) was used to release Ca2+ from the SR and to generate a tension transient. Each tension transient occurred after sequential immersion of the fiber bundles into five solutions: loading (uptake phase, [U]) and releasing (release phase, [R]). The height of free Ca2+-activated tension development of the contractile proteins, and the area of the tension transient generated by caffeine were assessed. (1) The direct free Ca2+-activated tension development of the contractile proteins was not significantly affected by ryanodine up to 0.1 mM, either at the submaximal or maximal free Ca2+ concentrations. (2) Ryanodine (1 nM-1 microM), in U, R, or in U and R, did not significantly change the immediate caffeine-induced tension transients. In the same preparation after ryanodine treatments, the second control caffeine-induced tension transients (C2, no ryanodine) were decreased in a dose-dependent manner (IC50 = 50 nM, 10 nM, 10 nM for R, U, and U and R, respectively). The depression caused by ryanodine on the SR was "activity"-dependent and not readily reversible. Total calcium content in the SR of C2 was not significantly changed by small quantities of ryanodine (less than 0.1 microM) and was decreased with greater amounts of ryanodine (greater than or equal to 0.1 microM). Thus, at low concentrations of ryanodine, the negative inotropic action is due to decrease Ca2+ release from the SR; at high concentration of ryanodine, it is due to decrease in calcium accumulation in the SR.

Alkaloids↗
PubMed1988

Mechanisms of ryanodine-induced depression of caffeine-induced tension transients in skinned striated rabbit muscle fibers.

Evidence suggests that ryanodine affects ligand-gated calcium channels in the sarcoplasmic reticulum (SR) resulting in depressed muscle contraction. In skinned fibers from striated muscle the effects of ryanodine were examined (1) on Ca2+ uptake and on Ca2+ release to differentiate whether the effects are on the pump or channel, and (2) during the tension transient, with ryanodine exposure at various times either simultaneous with or directly after exposure to caffeine. Of total calcium content in the SR, 25 mM caffeine released greater than 90% in papillary muscle (PM), approximately equal to 25% in soleus (SL), and approximately equal to 20% in adductor magnus (AM). Ryanodine (100 microM for 1-3 s for AM and SL; 1 microM for 7-10 s for PM), in the initial loading phase, did not significantly change, and in the initial release phase, markedly depressed the subsequent control caffeine-induced tension transients (C2) in all three muscle types. The depression increased with increasing time of exposure to ryanodine (10 microM) in the order of PM greater than AM greater than SL. Upon introduction of ryanodine after caffeine-induced tension transients, maximal depression was observed at half-maximum rise of the tension transient, followed by recovery of depression to completion in SL, and only partially in AM and PM at steady state of relaxation. The extent of recovery was in the order of SL greater than AM greater than PM. The data suggest that ryanodine affects Ca2+ releasing channel as a result of its binding to open channels.

Alkaloids↗
PubMed1987

Effects of ryanodine on skinned skeletal muscle fibers of the rabbit.

The mechanism(s) of ryanodine-induced contracture of skeletal muscle were studied in skinned fibers from soleus (SL) and adductor magnus (AM) (slow- and fast-twitch skeletal muscles) of rabbits. Pieces of SL or AM were homogenized (sarcolemma disrupted). Single fibers were dissected from the homogenate and mounted on photodiode force transducers. At concentrations 1-50 microM, ryanodine slightly but significantly increased the submaximal Ca2+-activated tension development of the contractile proteins in skinned fibers of AM but not of SL. Ryanodine in uptake phase or release phase increased caffeine-induced tension transients in the SR of both muscle types; however, no dose-response relation was found. Ryanodine greater than or equal to 1 microM decreased, however, the second control tension transients in a dose-dependent manner. The depression was nearly irreversible and "activity"-dependent. The concentrations of ryanodine that inhibited the second control tension transients by 50% were 10 microM and 5 microM for SL and AM, respectively, following ryanodine administration in the release phase, and 100 microM and 30 microM, respectively, for these preparations after the drug was present in the uptake phase. The quantity of calcium released from the SR by Triton X-100 and caffeine in the second control tension transient was unchanged by ryanodine at all concentrations tested when compared with that of the absence of ryanodine. The present findings suggest that the ability of ryanodine to increase immediate calcium release from the SR, and in AM but not SL, to increase the sensitivity of the contractile proteins to Ca2+ underlies the contracture caused by this agent in intact skeletal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1987

Comparison of the effects of halothane on newborn and adult rabbit myocardium.

The effect of halothane on myocardial contractility was studied in isolated right ventricular muscle preparations from newborn and adult rabbits. Right ventricular strips were mounted in oxygenated Krebs' solution and stimulated with supramaximal voltages at 1.0 Hz, while isometric force of contraction was continuously recorded. Halothane (0.4, 0.7, and 1.1%) caused a significant dose-dependent depression of both peak developed tension (42, 61, and 70%, respectively) and maximum rate of rise of isometric tension (40, 56, and 64%, respectively) of newborn myocardium. Newborn myocardial preparations exhibited approximately 20% greater depression of contractility than adult myocardium at each concentration studied (P less than 0.05), thus a parallel shift of the dose-response curves was observed. It was concluded that halothane exerts a potent depressant effect on newborn myocardium that is greater than that on adult myocardium. The depression effect of halothane on the newborn myocardium may contribute to its hypotensive effect in newborn infants.

Aging↗
PubMed1986

Intracellular mechanism of action of isoflurane and halothane on striated muscle of the rabbit.

Studies were conducted on the effects of isoflurane and halothane on intracellular mechanisms of striated muscle contraction: Ca2+ activation of the contractile proteins and Ca2+ uptake and release from the sarcoplasmic reticulum. Functionally skinned muscle fibers (sarcolemma disrupted by homogenization) from isolated papillary muscle (PM), soleus (SL) (slow-twitch skeletal muscle), and adductor magnus (AM) (fast-twitch skeletal muscle) of rabbits were mounted on a photodiode tension transducer. They were immersed in control solution (saturated with N2), then in test solution (saturated with anesthetic-N2 mixture), and in control solution again. The following two studies were carried out: 1) in the study of Ca2+ -activated tension development of the contractile proteins, free Ca2+ concentration in the bathing solution was controlled by the use of a high EGTA (7 mM), and 2) in the study of Ca2+ uptake and release from the sarcoplasmic reticulum (SR), Ca2+ was loaded into the SR and released with caffeine and the resulting tension transients were measured. Isoflurane (1-4%) decreased (6-9%) the maximal Ca2+ -activated tension development in PM and SL but more in PM than in SL. In AM, however, isoflurane and halothane (1-3%) produced no change. Isoflurane decreased submaximal Ca2+ -activated tension development in PM, but effected no change in it in SL. Isoflurane and halothane increased the tension development in AM to the extent of producing a shift to the left in the pCa-tension curves of less than or equal to 0.1 pCa unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interaction of halothane and verapamil in isolated papillary muscle.

The combined depressant effects of verapamil and halothane on myocardial contractility were studied using isolated papillary muscle from the rabbit. Verapamil alone (0.5 microM) significantly decreased peak developed tension (PDT) by 15 +/- 2%, time to peak tension (TPT) by 10 +/- 1%, and maximum rate of increase of tension (+dT/dt) by 5 +/- 1%, but not maximum rate of decrease of tension (-dT/dt). Halothane alone (0.8%) significantly decreased PDT by 56 +/- 2%, TPT by 11 +/- 2%, +dT/dt by 53 +/- 2%, and -dT/dt by 56 +/- 2%. During the exposure period, the combination of verapamil and halothane together produced a simple additive effect (no significant interaction effect by two-way analysis of variance), with PDT decreased by 68 +/- 2%, TPT by 20 +/- 3%, +dT/dt by 62 +/- 2%, and -dT/dt by 65 +/- 2%. The reversibility of halothane-induced depression was also studied. Peak developed tension showed complete reversibility 30 min after discontinuing halothane. In the presence of verapamil, however, the reversibility of halothane-induced depression was not complete, and significant residual depression of PDT (19 +/- 3%) was observed. We conclude that the acute depressant effect of verapamil plus halothane in isolated papillary muscle is additive, but reversibility of halothane-induced depression may be impaired or prolonged in the presence of verapamil.

Animals↗
PubMed1985

Effects of (+)-propranolol on intracellular mechanisms of contraction in striated muscle of the rabbit.

In functionally skinned muscle fibers from the rabbit, we studied the effect of propranolol on calcium activation of the contractile proteins and, in separate experiments, on calcium uptake and release from the sarcoplasmic reticulum (SR) while measuring physiological tension. Pieces from isolated papillary muscle (PM), soleus (SL) (slow-twitch skeletal muscle), and adductor magnus (AM) (fast-twitch skeletal muscle) were homogenized (sarcolemma disrupted). A fiber bundle from PM and single fibers from SL and AM were dissected from the homogenate and mounted on a photodiode tension transducer. To study Ca2+-activated tension development of the contractile proteins, we used high EGTA (7 mmol/l) to control the free calcium concentration. To study SR function, we used five different solutions to load the calcium into the SR and to release it from the SR with 25 mmol/l caffeine, thus producing a tension transient. In general, propranolol has similar mechanisms of action in the three muscle types. Propranolol (0.1-1.0 mmol/l) increased the submaximal calcium-activated tension development in all muscles but with PM = SL greater than AM, and this increase was correlated with increases in calcium binding to isolated troponin C. Propranolol increased the maximal calcium-activated tension development in PM and SL, but decreased that in AM. Propranolol at concentrations of 0.3-1.0 mmol/l decreased calcium uptake by the SR but did not change calcium release in any of the three muscles. In PM, however, propranolol at a concentration of 0.1 mmol/l increased calcium uptake by the SR. We conclude that propranolol induces decreases in muscle contraction mainly by decreasing calcium uptake by the SR.

Animals↗
PubMed1984

Salutary effects of nitrendipine, a new calcium entry blocker, in hemorrhagic shock.

Intracellular accumulation of calcium is thought to play an integral role in the progression of ischemic injury and cell death. We infused the calcium entry blocker, nitrendipine (1.5 micrograms/kg per min), into cats in order to investigate the importance of extracellular Ca2+ influx during hemorrhagic shock. Nitrendipine proved to be a potent hypotensive agent in sham shock cats when infused over a 4 h period (156 +/- 9 to 90 +/- 5 mm Hg) (P less than 0.01). However, in hemorrhaged animals, nitrendipine treatment maintained the post-reinfusion MABP at a significantly higher (P less than 0.01) value than untreated controls (79 +/- 5 vs. 51 +/- 4 mm Hg, respectively). Superior mesenteric artery flow (SMAF) for hemorrhaged animals treated with nitrendipine was significantly higher (9.8 +/- 1.4 ml/min per kg) (P less than 0.01) than that for untreated cats (4.2 +/- 0.4 ml/min per kg), at 2 h post reinfusion. There was no significant increase in SMAF during oligemia in the nitrendipine-treated animals. Nitrendipine was also found to significantly retard the appearance of cathepsin D in the plasma of hemorrhaged cats as well as reduce plasma proteolysis to values not significantly different from sham shock animals. Furthermore, myocardial depressant factor (MDF) activity in the plasma of nitrendipine-treated shock cats was not significantly different from sham shock animals, while the plasma MDF activity for shock cats receiving vehicle increased 3-fold (P less than 0.001). The beneficial effects for nitrendipine in hemorrhagic shock are likely due to both its vasodilator function and its ability to reduce intracellular Ca2+ accumulation during ischemia, thereby reducing disruption of cell membrane systems.

Animals↗
PubMed1984

Intracellular mechanism of quinidine action on muscle contraction. A comparison between rabbit cardiac and skeletal muscle.

The mechanism of quinidine action on rabbit cardiac and skeletal muscle was examined with "functionally skinned" muscle-fiber preparations. By using these preparations we could correlate measurements of muscle tension with the effect of quinidine on the Ca2+ activation of the contractile proteins and on the Ca2+ uptake and release from the sarcoplasmic reticulum (SR).

Animals↗
PubMed1984

Caffeine-induced calcium release from isolated sarcoplasmic reticulum of rabbit skeletal muscle.

The essential conditions for the Ca2+ releasing action of caffeine from isolated sarcoplasmic reticulum (SR) of rabbits were evaluated by an investigation into the effects of Ca2+, Mg2+, MgATP2-, and ATP concentration, ionic strength, and degree of loading. The heavy fraction (4,500 X g) of the reticulum was used. Except for the study on degree of loading, 0.2 mg protein X ml-1 SR was loaded actively with 0.02 mM 45CaCl2, resulting in greater than 90 nmol X mg protein -1 at steady state, and then the effects of various parameters with or without (control) caffeine were tested. It was found that (1) caffeine induces a transient, dose-dependent release of Ca2+, (2) the absolute amount of Ca2+ released by caffeine increases with the Ca2+ load of the SR, (3) increasing the ionic strength (mu) from 0.09 to 0.3 lowers the threshold concentration of caffeine, (4) the SR is refractory to a repeated challenge by a caffeine concentration causing maximal effect, (5) caffeine-induced Ca2+ release increases with increasing (a) external Ca2+ concentrations up to 5 microM total Ca2+ (or 3 microM free Ca2+) and (b) free ATP concentrations up to 0.45 mM, and (6) caffeine-induced Ca2+ release is not affected by changes of either the Mg2+ or the MgATP2- concentration.

Adenosine Triphosphate↗
PubMed1984

Role of AVP in maintenance of circulatory homeostasis during hemorrhagic shock.

Hemorrhagic hypotension produces significantly increased plasma arginine vasopression (AVP) concentrations. We have utilized a specific antagonist (AVP-A) of the pressor effects of endogenous AVP to investigate the role of this neurohypophyseal hormone on the pathogenesis of hemorrhagic shock. Infusion of the AVP-A (2 micrograms/kg bolus + 2 micrograms X kg-1 X h-1 infusion) into sham-shocked animals produced no significant changes in any of the observed experimental variables. Cats subjected to hemorrhagic shock given AVP-A had final superior mesenteric artery flow (SMAF) values significantly (P less than 0.05) higher than shock cats given vehicle (7.7 +/- 1.1 vs. 4.5 +/- 0.8 ml X kg-1 X min-1, respectively). Increases in postreinfusion plasma cathepsin D activities were significantly blunted in hemorrhaged animals treated with AVP-A (10.4 +/- 2.0 vs. 24.8 +/- 5.5 U/mg protein; P less than 0.05). Plasma proteolysis as well as the plasma accumulation of myocardial depressant factor (MDF) were also significantly modulated by AVP-A treatment in hemorrhaged animals. MDF activities were 75 +/- 6 and 53 +/- 4 U/ml (P less than 0.02) for shock cats given vehicle or AVP-A, respectively. However, these beneficial actions were not reflected in any significant improvement in postreinfusion mean arterial blood pressure (MABP). These findings suggest that endogenous AVP functions not only as a potent splanchnic vasoconstrictor but also as a key humoral factor in the maintenance of postreinfusion MABP, a profile that is different from the role of angiotensin II, the other major splanchnic vasoconstrictor, in shock.

Animals↗
PubMed1984

Differences in threshold for protamine toxicity in isolated atrial and ventricular tissue.

The inotropic and chronotropic effects of protamine sulfate on rabbit myocardium were studied using isolated preparations of atrial and ventricular tissue. Each tissue differed markedly in its susceptibility to depression of peak isometric developed tension. The threshold concentration for depression of tension was 0.022% for left atrium, 0.055% for right atrium, and 0.3% for right ventricular papillary muscle. Tension in the left atrial preparation increased 20% over control at a protamine concentration of 0.02%, but decreased to less than 30% of control at a concentration of 0.022%. Right atrial tissue tension decreased to 48% of control at a protamine concentration of 0.055% and then to 17% of control at a concentration of 0.6%. In papillary muscle, tension decreased to 64% of control at a concentration of 0.3% and then to 9% of control at a concentration of 0.35%. Thus a very steep dose-response curve was observed for each tissue. In the right atrium-sinoatrial node preparation, administration of protamine at concentrations of 0.05-0.06% produced intermittent atrial extrasystoles, but no significant change in overall rate of discharge. The narrow margin of safety of the protamine dose-response curve may provide a partial explanation for the precipitous nature of hypotensive episodes during clinical administration.

Animals↗