Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 14,15-beta-oxido analogue of proscillaridin A (HOE 040), in a dose 4 times higher showed equally positive-inotropic effect on the isolated guinea pig heart as did proscillaridin A. In the dog in vivo HOE 040 was equally positive-inotropic, as measured by the increase of dp/dt of the left ventricle of the heart, as proscillaridin A. In combination with aconitine, HOE 040 also in 4fold higher dose caused less cardiac fibrillation on the isolated guinea pig heart than did proscillaridin A. The dose of HOE 040 which by infusion in the guinea pig in vivo precipitates cardiac arrhythmias was 4 times higher than that of proscillaridin A, the lethal dose was 5 times higher. In dogs in vivo the dose of HOE 040 by infusion causing prolongation of PQ or cardiac arrhythmias, resp., was twice the dose necessary of proscillaridin A, the lethal dose was nearly 5 times higher. The decrease of cardiac activity in Rhesus monkeys amounted to 69% in 24 h, whereas proscillaridin A decreased cardiac activity only by 41% in 24 h. The absorption of HOE 040 from the duodenum of dogs anesthetized with pentobarbital amounted to 72%, whereas proscillaridin A is observed by only between 14 and 25%. The concentration of the drug HOE 040 in hearts of rats was twice, in the hearts of dogs 3 fold that of proscillaridin A. The concentrations of both drugs in the brain of rats and dogs were not different. In the biochemical test system in vitro the blocking effect of both drugs on the Na+K+-ATPase of ox brain was not different.
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PMID:[14,15-beta-oxido analog of proscillaridin (HOE 040). A new cardiac glycoside with low arrhythmic activity and greater absorption ratio]. 10

The myofibrillar changes of rat denervated soleus muscle were studied in the presence and in the absence of an antifibrillatory drug. After bilateral sciaticotomy, a concentrated solution of procainamide hydrochloride was steadily released, by way of a miniosmotic pump, in the space between the soleus and the gastrocnemius muscles of one leg. Fibrillation activity of soleus muscles was checked electromyografically at 3- to 5-day intervals. On the 21st day following denervation the muscles were excised, stained for adenosine triphosphatase activity and analysed for myosin heavy chain (MHC) isoforms. In the denervated-procainamide-treated muscles fibrillation was consistently (-75% on average) depressed in comparison to the contralateral denervated muscles. Type 1 (slow) fibres and MHC isoform were also significantly reduced, to the advantage of type 2A (fast) fibres and MHC isoform. The results support the view that denervation inactivity, like other kinds of muscle inactivity, favours the expression of fast type myofibrillar isoforms, and that this effect is counteracted, at least partially, by the spontaneous activity of the denervated muscle.
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PMID:Slow-to-fast transformation of denervated soleus muscle of the rat, in the presence of an antifibrillatory drug. 161 16

Electrophysiological and muscle histochemical studies of denervated muscle were performed simultaneously in order to determine the relationship between fibrillation potentials and muscle fiber type. Fibrillation potentials recorded in the soleus muscle 2 weeks after resection of the sciatic nerve revealed a lower firing rate than in the extensor digitorum longus (EDL) muscle of the same rats. The majority of muscle fibers stained for adenosine triphosphatase (ATPase) activity after preincubation at pH 9.4, 4.6, and 4.3 in the soleus muscle were type 1 fibers, while most of those in the EDL were of type 2. Moreover, one of the rats, which demonstrated no fibrillation potentials in the soleus muscle, was found to have no type 2A or 2B fibers histochemically, in the same soleus muscle. These findings suggest that fibrillation potentials may not originate in type 1 fibers.
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PMID:Fibrillation potentials do not originate in type 1 muscle fibers? 191 40

Emotional-painful stress in rats was shown to decrease insignificantly transmembrane cardiomyocyte potential (TCP) measured in isolated hearts. The recovery of TCP following its depression due to the preparation cooling was twice slower in stress-exposed than in control animals. This is in keeping with the data on stress-induced disturbances of Na, K-ATPase activity (an enzyme playing a leading role in TCP maintenance). It is suggested that the disturbance in cation pump function activity plays a certain role in the onset of arrhythmias and cardiac fibrillation during stress.
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PMID:[Effect of stress on the cardiomyocyte transmembrane potential of the working heart and its recovery after hypothermia]. 243 58

The present paper shows the arrhythmogenic effect of a direct induction of lipid peroxidation (LP) on isolated auricles; it is demonstrated that preendured stress potentiates this effect, while antioxidants prevent it. Subsequently, in studying the mechanism of the LP arrhythmogenic effect it was established that stress, like the LP induction, disorders the activity of Na, K-ATPase and accelerates thermodenaturation of this enzyme which plays a key role in maintaining the transmembrane potential and the electrical stability of the heart. Antioxidants prevent the enumerated shifts. Based on these data, the antioxidant BHT was successfully applied for prevention of the fall in cardiac fibrillation threshold in stress and experimental myocardial infarction, and also for prevention of cardiac fibrillation itself under acute ischemia and reoxygenation of the heart.
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PMID:The role of lipid peroxidation in pathogenesis of arrhythmias and prevention of cardiac fibrillation with antioxidants. 303 69

Risk for Atrial Fibrillation (AF), the most common human arrhythmia, has a major genetic component. The T-box transcription factor TBX5 influences human AF risk, and adult-specific Tbx5-mutant mice demonstrate spontaneous AF. We report that TBX5 is critical for cellular Ca²⁺ homeostasis, providing a molecular mechanism underlying the genetic implication of TBX5 in AF. We show that cardiomyocyte action potential (AP) abnormalities in Tbx5-deficient atrial cardiomyocytes are caused by a decreased sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2)-mediated SR calcium uptake which was balanced by enhanced trans-sarcolemmal calcium fluxes (calcium current and sodium/calcium exchanger), providing mechanisms for triggered activity. The AP defects, cardiomyocyte ectopy, and AF caused by TBX5 deficiency were rescued by phospholamban removal, which normalized SERCA function. These results directly link transcriptional control of SERCA2 activity, depressed SR Ca²⁺ sequestration, enhanced trans-sarcolemmal calcium fluxes, and AF, establishing a mechanism underlying the genetic basis for a Ca²⁺-dependent pathway for AF risk.
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PMID:A calcium transport mechanism for atrial fibrillation in Tbx5-mutant mice. 3089 5

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