title: Relation between cytosolic free Ca2+ concentration and the control of pyruvate dehydrogenase in isolated cardiac myocytes.
abstract: The proportion of pyruvate dehydrogenase existing in the active form (PDHA) in suspensions of unstimulated cardiac myocytes oxidizing glucose is approx. 30%. Depolarization of the cells with concentrations of K+ above physiological values leads to an increase in the content of PDHA. Overloading of the cells with Na+ by treatment with veratridine and ouabain gives the same result. Each of these interventions is shown in experiments with Quin 2-loaded myocytes to lead to an increase in cytosolic free Ca2+ concentration ([Ca2+]c). Treatment of the cells with Ruthenium Red, an inhibitor of Ca2+ transport into mitochondria, largely prevents an increase in PDHA in response to addition of KCl or of veratridine plus ouabain. Ruthenium Red does not attenuate the increase in [Ca2+]c that occurs under these conditions. By contrast, treatment of the cells with ryanodine, an inhibitor of sarcoplasmic-reticulum Ca2+ transport and therefore of contraction, does not diminish the response of PDHA content to agents which raise [Ca2+]c; nor does loading of the cells with the Ca2+-chelating agent Quin 2, which also prevents contraction, at appropriate concentrations. It is concluded that an increase in [Ca2+]c causes an increase in PDHA content of cardiac myocytes independently of an increase in mechanical work. In the normal physiological situation the activation of dehydrogenases by Ca2+ is thought to help to maintain the balance of energy supply and demand during periods of increased work-load, which are associated with an increased myoplasmic [Ca2+]c.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014701:Veratridine / Q000494:pharmacology
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D012430:Ruthenium Red; D012433:Ryanodine; D010042:Ouabain; D011189:Potassium Chloride; D014701:Veratridine; D002118:Calcium