Biomedical subjects

M J Su

Publications and source records attributed to M J Su.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Comparison of the electromechanical responsiveness of alpha-1-adrenoceptor stimulation in ventricles of normal and cardiomyopathic hamsters.

Alterations in alpha(1)-adrenoceptor (alpha(1)AR) density and related signal transduction proteins were reported in cardiomyopathic hearts in the failing stage. The electromechanical modification of alpha(1)-adrenergic stimulation in the failing heart is unclear. The present study compares the alpha(1)AR-stimulated electromechanical response in failing ventricles of genetically cardiomyopathic BIO 14.6 hamsters (280-320 days old) with that in age-matched normal Syrian hamsters. The action potential was recorded with a conventional microelectrode technique, and twitch force was measured with a transducer. In the presence of propranolol, phenylephrine increased the contraction and prolonged the action potential duration (APD) to similar values in ventricles of both strains, despite a prolonged basal APD in cardiomyopathic ventricles. The positive inotropism stimulated by phenylephrine was inhibited by staurosporine, and was potentiated by 4 beta-phorbol-12,13-dibutyrate (PDBu) in both strains. The maximum positive inotropic effect of phenylephrine in PDBu-treated ventricles of normal hamsters was significantly greater than that in BIO 14.6 hamsters. The effects of phenylephrine on the ventricular force-frequency relationship and on the mechanical restitution in both normal and BIO 14.6 strain hamsters were examined. The uniform negative force-frequency relationship and the altered mechanical restitution reveal a defect of intracellular Ca(2+) handling in cardiomyopathic BIO 14.6 hamsters. alpha(1)-Adrenergic modulation cannot convert the defective properties in the model of the failing heart. Nevertheless, phenylephrine decreased post-rest potentiation in short rest periods, and enhanced post-rest decay after longer resting periods. The results indicate that alpha(1)-adrenergic action enhances a gradual loss of Ca(2+) from the sarcoplasmic reticulum, although its action in prolonging the APD can indirectly increase the influx of Ca(2+).

Action Potentials↗

PubMedDate not supplied

Further evidence that extrinsic acetylcholine acts preferentially on extrajunctional receptors in the chick biventer cervicis muscle.

The specificity of action of extrinsic acetylcholine on extrajunctional and junctional receptors in the chick biventer cervicis muscle was studied by determining its ability to protect the responses evoked by acetylcholine and by tetanic nerve stimulation from the blockade by alpha-bungarotoxin, an irreversible binding agent of acetylcholine receptors. At concentrations of 50-100 mug/ml, acetylcholine caused a desensitization to extrinsic acetylcholine but not to nerve stimulation and protected only the contractile response to extrinsic acetylcholine from the toxin blockade whereas neither the response to tetanic nerve stimulation nor the endplate potentials were protected. For the protection of the latter, higher concentrations of acetylcholine were needed. In the presence of physostigmine, a concentration of acetylcholine as low as 10 mug/ml protected the endplate potentials from the toxin blockade. By contrast, d-tubocurarine protected the tetanic contraction and the endplate potentials induced by nerve stimulation at a concentration which produced the same protection of acetylcholine-induced contraction as that produced by 50-100 mug/ml acetylcholine. These results indicate that in contrast to d-tubocurarine, extrinsic acetylcholine at low concentrations acts preferentially on the extrajunctional receptors in the absence of an anticholinesterase.

Acetylcholine↗

PubMedDate not supplied

Identification of opioid receptors in the sympathetic and parasympathetic nerves of guinea-pig atria.

The opioid receptor subtypes of autonomic nerves of guinea-pig atria were elucidated by monitoring the effects of selective opioid receptor agonists on the negative and positive inotropic responses associated with the stimulation of the parasympathetic and sympathetic nerves, respectively. The positive inotropic effect, evoked by electrical field stimulation (2 Hz) was strongly reduced by the selective OP2-opioid receptor agonists U-50488 and U-69593, but partly by the OP3-opioid receptor agonist morphine. This effect of U-50488 and U-69593 were reversed by the selective OP2-opioid receptor antagonist nor-BNI. The effect of morphine was partly reversed by naloxone, whereas OP1-opioid receptor agonists, BW373 U86 and DPDPE, were ineffective. On the other hand, the negative inotropic response to electrical field stimulation was not affected by opioid receptor agonists. These results suggest that the noradrenaline release from cardiac sympathetic nerves of guinea-pig could be modulated, mainly by the OP2-opioid receptor, however, the acetylcholine release from cardiac parasympathetic nerves is not modulated by opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMedDate not supplied

Inward rectifier and delayed outward potassium currents in isolated guinea-pig ventricular myocytes: maturation and its role in repolarization.

In accord with previous reports, we have found that action potentials triggered from isolated mature (> 1 month) guinea-pig ventricular myocytes showed a longer duration than those from the neonate (< 1 day). A whole-cell voltage-clamp technique has been used to identify the postnatal changes of inward rectifier (Ikl) and delayed outward potassium currents (Ik), which may be related to the action potential transition. Our results have shown that the degree of maturation of the neonatal guinea-pig is much advanced, as compared to neonatal rabbits and rats. Slope conductance (1230 +/- 110 pS/pF, n = 10, for neonatal, and 1450 +/- 450 pS/pF, n = 10, for mature guinea-pig, p > 0.05) and the inward rectification occurring over a potential range from -50 to -10 mV were relatively similar between the neonatal and mature guinea-pig myocytes. But, the slope conductance of Ik was significantly greater in neonatal (702 +/- 80 pS/pF, n = 10) guinea-pig myocytes than in the mature (194 +/- 23 pS/pF, n = 10, p < 0.01). Therefore, we suggest that (1) the maturation of Ik appears later than that of Ikl, (2) age-related decrease of the slope conductance of Ik could contribute to an age-related lengthening of the action potential duration.

Action Potentials↗