Effect of platelet activating factor on guinea-pig papillary muscle

Summary Platelet activating factor (PAF) induces a biphasic effect on guinea-pig papillary muscle: 1. a transient positive inotropic effect preceded by an increase in action potential duration (APD); 2. a marked negative effect on inotropism and on APD. Since Ca⁺⁺ slow action potentials were initially enhanced by PAF and then markedly depressed, it is suggested that PAF specifically interferes with the Ca⁺⁺ slow channel.     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine.

Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.     

Extracellular calcium ions modify the effects of Anemonia sulcata toxin (ATX II) in guinea-pig papillary muscles

In isolated guinea-pig papillary muscle ATX II prolonged the action potential duration to a lesser extent at high extracellular Ca++-concentrations. This is interpreted as an interference of Ca++ with ATX II-binding sites.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport.

Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca++-ATPase activity and Ca++-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg++-, Ca++-and (Na+ + K+)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca++-ATPase activity, is not related to Ca++-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Manganese action potentials in mammalian cardiac muscle.

The membrane potential in guinea-pig's papillary muscles from right ventricle was recorded by glass microelectrodes and stimulation was effected by current pulses applied through a sucrose-gap. Action potentials with overshoot were recorded in the solution lacking Na+ and Ca++ but containing 2-95 mM Mn++. The overshoot was increased with the increase of [Mn++]o by about 30 mV/decade. Similar Mn++ dependent action potentials were also obtained in Na-free solution containing 0.6 mM Ca++. The results indicate that Mn inward current is sufficient to generate action potentials in cardiac muscle.     

Isoprenaline-like effects of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on mechanical, biochemical and electrophysiological parameters in the mammalian heart

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and beta-adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP.     

Influence of ethanol on calcium, inositol phospholipids and intracellular signalling mechanisms

Studies have implicated Ca++ in the actions of ethanol at many biochemical levels. Calcium as a major intracellular messenger in the central nervous system is involved in many processes, including protein phosphorylation enzyme activation and secretion of hormones and neurotransmitters. The control of intracellular calcium, therefore, represents a major step by which neuronal cells regulate their activities. The present review focuses on three primary areas which influence intracellular calcium levels; voltage-dependent Ca++ channels, receptor-mediated inositol phospholipid hydrolysis, and Ca++/Mg++-ATPase, the high affinity membrane Ca++ pump. Current research suggests that a subtype of the voltage-dependent Ca++ channel, the dihydropyridine-sensitive Ca++ channel, is uniquely sensitive to acute and chronic ethanol treatment. Acute exposure inhibits, while chronic ethanol exposure increases 45Ca++-influx and [3H]dihydropyridine receptor binding sites. In addition, acute and chronic exposure to ethanol inhibits, then increases Ca++/Mg++-ATPase activity in neuronal membranes. Changes in Ca++ channel and Ca++/Mg++-ATPase activity following chronic ethanol may occur as an adaptation process to increase Ca++ availability for intracellular processes. Since receptor-dependent inositol phospholipid hydrolysis is enhanced after chronic ethanol treatment, subsequent activation of protein kinase-C may also be involved in the adaptation process and may indicate increased coupling for receptor-dependent changes in Ca++/Mg++-ATPase activity. The increased sensitivity of three Ca++-dependent processes suggest that adaptation to chronic ethanol exposure may involve coupling of one or more of these processes to receptor-mediated events.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dtmax) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dtmax and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.     

Immunochemical evidence for the specific binding of putrescine to plasma proteins including fibronectin

Human plasma contains proteins capable of binding 14C putrescine by the action of Ca++ activated transglutaminase. These proteins have molecular weights from 32 to 220 K and above. One of these (with a molecular weight of 220 K) has been identified as fibronectin by the use of an antifibronectin antiserum. Evidence for a protein with a molecular weight identical to that of fibronectin has been obtained on PAGE analysis of the precipitate formed on incubating human serum with antipolyamine antiserum.     

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools

Urethane (1 X 10(-2) - 1 X 10(-1) M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline. - Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect 'in vivo' cannot be explained by a direct interference of urethane with beta-adrenoceptors at cardiac level.     

Effects of starvation and Ca++ on glucose-induced accumulation of cyclic 3',5'-AMP in pancreatic islets.

Exposure to glucose in the presence of 3-isobutyl-1-methylxanthine leads to accumulation of cAMP in islets microdissected from ob/ob mice. This process is dependent on extracellular Ca++ but differs markedly from the glucose action on insulin release in the same in vitro system in disappearing after 18 h of starvation.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Summary Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dt_max) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dt_max and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.Supported by the Deutsche Forschungsgemeinschaft (Na 105/5-5) and by the Fonds der Chemischen Industrie. Author to whom reprint requests should be addressed. We thank Mrs. Johanna Rupp for expert technical help. We also thank one referee for suggesting the experiments depicted in figure 4.     

Increase in spontaneous beating frequency in rat heart cells cultured in homologous serum]

Rat serum at different concentrations added to cultured Rat heart cells medium increased spontaneous beating frequency of myoblasts. This increase occurred instantaneously and lasted more than 24 hrs. It was related to the serum concentration used. Electrophysiological recording showed a decrease in the iso-electric phase duration of membrane potential, with no change in action potential. In spite of the beating frequency increase, cells remained sensitive to the chronotrope positive action induced by Isoprenaline. There was no difference between male and female sera. The global results could partly be explained by the action of Ca++ in Rat serum.     

Role of calcium in the histamine release induced by D-galactosamine from rat mast cells

Rat peritoneal mast cells were isolated and purified by differential centrifugation in Ficoll. Cells pooled from three to four rats were suspended at approximately 10(6) cells/ml in a buffered salt solution and incubated for 1 h at 37 degrees C in 300 microliter volumes in the absence or presence (9 X 10(-4) M) of calcium chloride. Addition of D-galactosamine hydrochloride (DGM; 2.8 X 10(-4)M) caused (in addition to basal release) a mean +/- SEM percent histamine release of 15.7 +/- 5.2 in the presence of Ca++ and 19 +/- 4.9 in the absence of Ca++ (p greater than 0.05). It is suggested that D-galactosamine does not require extracellular Ca++ for the release of histamine from the rat mast cell.     

The effects of diverse agents (Ca++ and K++ ionophores, organomercurials, dithiols, colchicine, and cytochalasin B) on the maturation and differentiation without cleavage in Chaetopterus eggs]

Induction of maturation in Chaetopterus oocytes requires the presence of Ca++ ions in the medium, but differentiation without cleavage can proceed in the absence of this cation. The Ca++ ionophore A 23187 induces both maturation and the cortical reaction provided that Ca++ ions are present in the medium differentiation without cleavage may follow. Valinomycin slowly induces germinal vesicle breakdown, which is followed by a sharp segregation between hyaloplasm and yolk. PHMPS, but not DTT, induces maturation. Differentiation without cleavage is more sensitive to colchicin than to cytochalasin B.     

Consequences of acute ischemia for the electrical and mechanical function of the ventricular myocardium. A brief review

Reduction or interruption of the blood supply to the myocardium leads to marked disturbances of electrical and mechanical function within a few seconds. Electrical dysfunction is characterized by an initial depolarization of the resting membrane, and a decrease of the amplitude, the upstroke velocity and the duration of the action potential. Both depolarization and depression of the action potential are closely associated with intracellular metabolic acidosis. After this initial phase, electrical cell-to-cell uncoupling develops, probably as a consequence of increased cytosolic free [Ca++]. Mechanical dysfunction is characterized by a dissociation of the initial decrease of active force development from the subsequent ischemic contracture. Active force development in acute ischemia is inhibited by the accumulation of ischemic metabolic products (H+, inorganic phosphate (Pi), Mg++) but not by a marked decrease of [ATP]. The subsequent ischemic contracture is probably initiated by release of Ca++ from intracellular stores. This release causes rapid consumption of ATP and the development of rigor within 1-2 minutes.     

A possible physiochemical explanation for the psychotherapeutic role of lithium]

Manic-depressive psychosis could result from degradation of lipids in some neuronic membranes. This degradation could lead to fatty acids, which when ionized in the external medium would definitely disappear. If this medium contains Li+, a poorly soluble precipitate would be formed with the fatty anions. This precipitate, impermeable to its formative ions would slow down the dissipation of the fatty acids and thus facilitate the resynthesis of the original lipids. Ca++ cations being divalent could not play the same role.     

The effect of nifedipine and verapamil on KC1-induced rhythmic contractions of guinea pig ureter in vitro

Addition of KC1 (40 mM) produced rhythmic contractions of guinea-pig ureters in vitro which were unaffected by phentolamine, atropine or tetrodotoxin. KC1 failed to elicit rhythmic contractions of ureters incubated in a Krebs solution with no added Ca++; in these conditions the addition of CaC12 in concentrations of 1.5 mM, or higher, produced rhythmic contractions whose frequency, but not amplitude, was proportional to CaC12 concentration in the bathing medium. EDTA reduced the frequency of KC1-induced rhythmic contractions without affecting their amplitude. Nifedipine and verapamil reduced both the frequency and the amplitude of KC1-induced rhythmic contraction; verapamil was more effective than nifedipine in reducing their amplitude. Urethane reduced the amplitude without significantly affecting the frequency of KC1-induced rhythmic contractions. An increase in the extracellular Ca++ concentration reverted the suppressive effect of all drugs under study. These results suggest that an influx of Ca++ from the extracellular space is responsible for the initiation of KC1-induced rhythmic contractions and is involved in the mechanism(s) which regulates their frequency, but that a separate mechanism regulates their amplitude.     

Contribution of divalent cations to the maintenance of membrane potentials in the oocytes of Pleurodeles waltlii Michah (Amphibia, Urodela)]

When the external concentration of Ca and Mg is changed, the oocyte membrane potential, in the Urodela Amphibian: Pleurodeles waltlii, is not significantly modified. The addition of chelator agents, EGTA and EDTA in Ca, Mg free Steinberg solution promotes a membrane depolarisation and the rise of membrane conductance. It is concluded that divalent ions Ca++ and Mg++ are needed to maintain a potential difference between internal and external medium of the oocyte.     

Über die Wirkung von Prostaglandin E1 auf den Ca-Haushalt isolierter Meerschweinchenherzen

Summary The stimulatory effect of PGE₁ on different functions of isolated guinea-pig hearts (Langendorff method, Tyrode solution) was coupled with an increase in the rate of⁴⁵Ca uptake from the perfusion medium. The total myocardial Ca content and the amount of exchangeable cellular Ca were not affected. This action of PGE₁ on the myocardial Ca metabolism seems to be related to the positive inotropic action of PGE₁ and can most probably be explained by an increase in the membrane permeability to Ca ions (similar to the action of epinephrine).