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Biomedical subjects

M E Saxon

Publications and source records attributed to M E Saxon.

14 recordsLinked to original sources
PubMed1989

Positive inotropic effect of ryanodine on rabbit ventricular muscle: dependence on the intracellular calcium load.

Two types of electrical and mechanical responses to 1 mumol/l ryanodine, depending on the intracellular calcium load, were observed in rabbit papillary muscles. In a normal calcium solution, ryanodine induced a transient decline followed by a stable increase in the developed force (by 20 +/- 5% of the pretreatment level; n = 30) and prolonged the action potential (AP). The positive ryanodine response showed an increased time-to-peak force and was completely suppressed by 2 mumol/l nifedipine, partially blocked by 50 mumol/l tetracaine (Ca2+ release blocker), but greatly potentiated by 20 mmol/l CsCl or (-) Bay R 5414 which prolonged the AP. The prolonged time-to-peak force of the positive ryanodine response was shortened by procedures raising the content of Ca2+ in the sarcoplasmic reticulum (SR). It is suggested that the initial decline in the force amplitude results from Ca2+ leakage from the SR which is further compensated for by an elevation of both the transmembrane Ca2+ entry and intracellular Ca2+ release. In calcium overloaded myocardium, 1 mumol/l ryanodine caused irreversible contracture and dramatic AP shortening, explained by a massive Ca2+ release from the overloaded SR into the cytoplasm. It is concluded that the calcium content in the SR is the main modulator of the electrical and mechanical effects of ryanodine in ventricular myocardium.

Alkaloids↗
PubMed1988

Ryanodine in low concentrations is a Ca-release stimulator rather than inhibitor in rat myocardium.

The effects of ryanodine on negative force staircase and potentiated rested-state contraction (RC) in rat myocardium were compared to the action of Ca release stimulator (caffeine) and inhibitors (local anesthetics). Only low ryanodine concentrations (0.1-0.5 mumol/l) were found to reverse anomalous mechanical patterns in rat myocardium to similar to those as generally observed in other mammalian species. Ryanodine-induced positive staircase and a weak RC were potentiated by noradrenaline. The results obtained seem to characterize ryanodine as a Ca2+ release stimulator rather than an inhibitor in this species and suggest different molecular substrates for ryanodine and caffeine inotropy in rat myocardium.

Alkaloids↗
PubMed1985

Dihydropyridine Ca2+ agonists and channel blockers interact in the opposite manner with photogenerated unpaired electrons.

Interaction of Ca2+-channel antagonists (felodipine, ryocidil, verapamil, diltiazem) and agonists (dihydropyridine derivatives Bay K 8644 and CGP 28392) was studied by the methods of absorption spectroscopy. Ca2+-channel antagonists were found to act as electron donors, the agonists being electron acceptors in the interaction with dye free radicals in solution. Redox transitions in channel-forming protein were proposed as a possible mechanism of the modulation of channel activity by the compounds tested.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1984

Anomalous response of rabbit papillary muscles to depolarising current: the possible role of the transient outward current. A pharmacological analysis.

Rabbit papillary muscles under current depolarization generate an anomalous double action potential (AP) instead of a usual repetitive activity characteristic of myocardial fibres of different mammalian species. The mechanism of the double AP consisting of a spike-like and a delayed slow component was analysed using pharmacological approach. No changes in the anomalous double AP were observed in the presence of Cs ions. This contrasted with the inhibitory action of 4-aminopyridine (4-Apy). High sensitivity of the phenomenon to 4-APy suggests a contribution of the transient outward current, previously postulated for rabbit working myocardial fibres, to account for the double AP.

4-Aminopyridine↗
PubMed1982

Calmodulin-dependent regulation of calcium-activated outward current in frog atrial membrane.

The steady-state outward current underlying the inward-going rectification in frog atrial fibers has been studied by the double sucrose gap technique. Similar to the case in sheep Purkinje fibers (18,19), the inward rectifying potassium channels in frog atrium are blocked by cesium (5 mM) and activated by increasing cytosolic calcium concentration (replacing 30% of the Na by sucrose). It was shown that trifluoperazine (5 x 10(-6) M), a widely used blocker of the Ca-calmodulin complex, inhibits the inward rectifying potassium channels. Diphenylhydantoin (5 x 10(-6) M), a putative inhibitor of Ca-calmodulin-mediated membrane phosphorylation produces a similar action. The inhibitory action of both blockers is not manifested after preliminary Cs+ (5 mM) exposure. The data obtained suggest that calcium activates the inward rectifying potassium channels in frog atrial fibers via Ca-calmodulin regulatory phosphorylation of the membrane proteins.

Animals↗
PubMed1982

Mechanism of plateau loss in rabbit papillary muscle after a short rest. Role of outward current.

Shortening of the first action potential plateau phase and potentiation of isometric contraction are simultaneously found in rabbit papillary muscle after 1 min of rest. The ionic nature of these events was investigated. Shortening of the plateau phase is not markedly prevented by activators of the slow inward current (5'-guanyl imidodiphosphate, 10(-5) M plus isoproterenol, 10(-7) M) but is completely eliminated by potassium current blockade with 4-aminopyridine (2 X 10(-4) M). The latter suggests the key role of the outward current increase in plateau phase shortening. It is further potentiated by high external K+ and Ca2+ as well as by ouabain 5 X 10(-7) M. It is concluded that simultaneous alteration of mechanical and electrical activity after rest might be related to accumulation of Ca2+ inside the cardiac cell and K+ outside it as the result of sodium pump inhibition in quiescent rabbit papillary muscle.

4-Aminopyridine↗
PubMed1982

The rest-dependent depression of action potential duration in rabbit myocardium and the possible role of the transient outward current. A pharmacological analysis.

A pharmacological approach has been used to investigate the mechanism of the action potential depression after a 1 min rest in rabbit myocardium. This paradoxical depression was not prevented by potentiators of the slow inward current (isoproterenol and 5'-guanylylimidodiphosphate). This depression was completely removed by a specific blocker of the transient outward current, 4-aminopyridine. It appears reasonable to assume that rabbit ventricular fibers have a transient outward current and the activation of this current coupled to the masking of the slow inward current probably accounts for the depression of the rested action potential plateau phase.

Action Potentials↗
PubMed1981

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity.

Low voltage myocardial automaticity (LVA) was investigated by pharmacological modulations of the presynaptic and postsynaptic processes. The sensitivity of LVA both to inhibitor and stimulator of neurotransmitter release suggests its involvement in LVA genesis. Moreover, LVA is blocked by the inhibition of the cyclic AMP system, supporting the participation of the c-AMP-dependent membrane phosphorylation in calcium-mediated cardiac electrogenesis.

Adult↗
PubMedDate not supplied

Stabilizing effect of antioxidants and inhibitors of prostaglandin synthesis on after-contractions in Ca2+-overloaded myocardium.

Ca2+ overload followed by after-contractions was induced by perfusion of mammalian papillary muscles with O-K0+, high Ca2+ solution. The effect of lipotrophic agents (dexamethasone, indomethacin) or free radical scavengers (alpha-tocopherol, reduced glutathione, synthetic antioxidant) was tested at different stages of Ca2+ overloading processes. All the agents tested proved to be effective in attenuating the after-contractions. Activation of lipid peroxidation has been suggested as one of the possible molecular events underlying mechanical destabilization of Ca2+-overloaded myocardium.

Animals↗
PubMedDate not supplied

The possible role of phospholipase A2 in cardiac membrane destabilization under calcium overload conditions.

The mechanism of spontaneous diastolic depolarizations induced by different Ca2+ overloading conditions (ouabain toxicity, calcium ionophore A23187, O-K, high Ca2+ solution) in mammalian working myocardium fibres was studied with conventional microelectrode technique and pharmacological approach. Antagonistic properties of antiphospholipase-A2 (PL A2)-active compounds (dexamethasone and indomethacin) were tested. Membrane oscillations in Ca2+ overload conditions were shown to be eliminated or largely protected by both anti-inflammatory agents. There was no influence of the compounds on electrical parameters and ion currents in intact mammalian and amphibian myocardium. The data obtained suggested that modulation of Ca2+-dependent PL A2 activity may contribute significantly to membrane destabilization due to Ca2+ overload of cardiac cells. An analogous membrane destabilizing action of exogenous PL A2 observed in Langendorff-perfused guinea pig heart is in favour of the hypothesis introduced.

Animals↗