The 'calcium sensitising' effects of ORG30029 in saponin- or Triton-skinned rat cardiac muscle

التفاصيل البيبلوغرافية
العنوان: The 'calcium sensitising' effects of ORG30029 in saponin- or Triton-skinned rat cardiac muscle
المؤلفون: D S Steele, David J. Miller
المصدر: British journal of pharmacology. 100(4)
سنة النشر: 1990
مصطلحات موضوعية: medicine.medical_specialty, Cardiotonic Agents, Muscle Relaxation, Cmax, chemistry.chemical_element, Calcium, In Vitro Techniques, Polyethylene Glycols, Contractility, chemistry.chemical_compound, Internal medicine, Caffeine, medicine, Animals, Organic Chemicals, Pharmacology, Chemistry, Myocardium, Cardiac muscle, Heart, Saponins, Myocardial Contraction, Rats, Sarcoplasmic Reticulum, Endocrinology, Muscle relaxation, medicine.anatomical_structure, Mechanism of action, Ventricle, medicine.symptom, Research Article
الوصف: 1. The effects of a range of concentrations of ORG30029 (1 microM to 1 mM) were investigated on fully (Triton-treated) or selectively (saponin-treated) 'skinned' ventricle trabeculae from rat. The Ca-sensitivity was increased by 100 microM and amounted to a mean reduction in the Ca2+ necessary for half-maximal activation (1/Kapp) of 0.174 +/- 0.053 (mean +/- s.e.mean) pCa units. ORG30029 (50 microM) gave a smaller mean shift of 0.05 +/- 0.016 pCa units. A slight shallowing of the relationship between -log[Ca2+] (pCa) and steady-state tension was also generally found (mean Hill exponent reduction 0.37 +/- 0.28 at 100 microM). 2. The Ca-sensitizing action altered in a dose-dependent fashion. Judged by the ability to enhance force from an initial level of activation of 10-20% of maximum Ca-activated force (Cmax), the first significant effects occurred near 10 microM and continued to increase at 1 mM. 3. A small (3.7 +/- 1.1%) but consistent increase in Cmax was produced by ORG30029 at 100 microM. Much larger increases were produced by the drug at higher concentrations (up to 20-50% at 1 mM). 4. The consequence of these changes is that at levels of activation likely to occur in the heart, the absolute increase in force by 100 microM ORG30029 was considerable: it amounted to a 150-200% increase at a [Ca2+] producing 20% at Cmax. At this drug concentration virtually all the effect was due to Ca-sensitizing rather than increasing Cmax. 5. In the saponin-treated preparations, at concentrations up to 1 mM, ORG30029 did not release Ca from the sarcoplasmic reticulum, as indicated by the failure to evoke contracture under conditions where caffeine induced large responses. 6. At 100 microM, ORG30029 potentiated the transient, caffeine-induced contracture (saponin-treated preparation) to an extent consistent with the Ca-sensitizing effect seen under conditions of steady-state tension development.
تدمد: 0007-1188
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83cba8cfdf91af25dc2d2b38a64bf9ee
https://pubmed.ncbi.nlm.nih.gov/2207503
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....83cba8cfdf91af25dc2d2b38a64bf9ee
قاعدة البيانات: OpenAIRE