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Cardiac myosins: Distribution of myosin heavy chain isoforms in ordinary myocardium and conduction tissue
j Mol Cell Cardiol 17 (Supplement 3) (1985)
97SUBTYPES OF DIGITALIS RECEPTORS.
T. Godfraind, J. Ghysel-Burton, M. Finet and F. Noel. Laboratoire de Pharmacodynamie G~n~rale et de Pharmacologie, Universit~ Catholique de Louvain, av. E. Mounier, 73, UCL 7350, 1200 Brussels, Belgium. Identification of cardiac glycosides receptors has been performed using intact tissues or microsomal preparations by measuring the binding of radioactive ouabain or of other derivatives. In guinea-pig atria, we have identified a high affinity, low capacity binding of ouabain in the nanomolar range (! i0.000 receptors/cell) and a low affinity, high capacity binding in the micromolar range (• I00.000 receptors/cell). There are several experimental observations indicating that high and low affinity binding sites are related to two different Na-,K--ATPases with different affinities for cardiac glycosides and for KC1. For a given species, the relative importance of high and low affinity sites vary according to the anatomical part of the heart. For instance, rat heart ventricles contain more high affinity binding sites than rat atria. Furthermore, the ratio between high and low ouabain binding sites affinities is different in different species : it is equal to 60-70 in rat heart microsomes and to 7 in human heart microsomes. The interaction of ouabain with both receptors types is responsible for the inotropic effect, part of which is antagonized by dihydroouabain.
98PHENOTYPIC CHANGES OF THE HEART DURING DEVELOPMENT AND UNDER PATHOLOGICAL SITUATIONS. K. Schwartz, JL. Samuel, JJ. Mercadier, D. de la Bastie, AM. Lompr4, B. Swynghedauw and L. Rappaport. U 127 INSERM, Paris, France. The ability of the myocardium to respond to physiological and pathological demands depends to an unknown extent on the plasticity of expression of contractile proteins multigene families and on the cytoskeleton organization. We have studied the species and tissue specificities and the time-course of several phenotypic changes. Transitions between a and ~ myosin heavy chains (MHC) seem to be regulated by the same stimuli in atria and ventricles although the extent of regulation is quite different for the two tissues, depending both on the initial phenotype and on the stimulus : severe hypothyroidism in rat affects mardkedly the ventricles and only slightly the atria. In contrast, chronic mechanical overloads are characterized both in rat ventricles and in human atria by significant shifts to ~ M H C (up to 80 % of total myosin). Ventricular isoactins and cytoskeletal organization (microtubules, desmin) also vary in rats in systolic overloads, but in contrast to the isomyosin changes, the responses are transitory. These results demonstrate that i) the pattern of expression of the different cardiac genes are not regulated in a coordinate fashion and ii) the myocardium responds to mechanical stimuli by two mechanisms, one transitory perhaps related to cardiac growth, and one non-transitory perhaps related to the production of new proteins best suited for the new environmental situation.
99CARDIAC MYOSINS: DISTRIBUTION OF MYOSIN HEAVY CHAIN ISOFORMS IN ORDINARY MYOCARDIUM AND CONDUCTION TISSUE. S. Schiaffino, L. Gorza, S. Sartore, L. Saggin. I n s t i t u t e of General Pathology, University of Padova, Padova, I t a l y . Polyclonal and monoclonal antibodies reacting s p e c i f i c a l l y with sarcomeric myosin heavy chains (MHCs) have been used to study the d i s t r i b u t i o n of d i f f e r e n t myosin isoforms in the mammalian heart. Three main types of MHCs have been identified: I) ~-MHC, the predominant form in the a t r i a l myocardium, 2) ~-MHC, which in large mammals is the major form in the v e n t r i c u l a r myocardium, and 3) nodal-MHC, a d i s t i n c t isoform s p e c i f i c a l l y localized in muscle c e l l s of the s i n o - a t r i a l and a t r i o - v e n t r i c u l a r nodes. In the bovine heart nodal-MHC appears to be a n t i g e n i c a l l y s i m i l a r but not i d e n t i c a l to MHCs present in f e t a l skeletal muscle. Immunoflurescence and immunoperoxidase studies show marked c e l l u l a r heterogeneity in myosin composition of nodal and perinodal tissue and internodal t r a c t s . The functional significance of regional variations in the d i s t r i b u t i o n of MHC isoforms in the mammalian heart w i l l be discussed.
97SUBTYPES OF DIGITALIS RECEPTORS.
T. Godfraind, J. Ghysel-Burton, M. Finet and F. Noel. Laboratoire de Pharmacodynamie G~n~rale et de Pharmacologie, Universit~ Catholique de Louvain, av. E. Mounier, 73, UCL 7350, 1200 Brussels, Belgium. Identification of cardiac glycosides receptors has been performed using intact tissues or microsomal preparations by measuring the binding of radioactive ouabain or of other derivatives. In guinea-pig atria, we have identified a high affinity, low capacity binding of ouabain in the nanomolar range (! i0.000 receptors/cell) and a low affinity, high capacity binding in the micromolar range (• I00.000 receptors/cell). There are several experimental observations indicating that high and low affinity binding sites are related to two different Na-,K--ATPases with different affinities for cardiac glycosides and for KC1. For a given species, the relative importance of high and low affinity sites vary according to the anatomical part of the heart. For instance, rat heart ventricles contain more high affinity binding sites than rat atria. Furthermore, the ratio between high and low ouabain binding sites affinities is different in different species : it is equal to 60-70 in rat heart microsomes and to 7 in human heart microsomes. The interaction of ouabain with both receptors types is responsible for the inotropic effect, part of which is antagonized by dihydroouabain.
98PHENOTYPIC CHANGES OF THE HEART DURING DEVELOPMENT AND UNDER PATHOLOGICAL SITUATIONS. K. Schwartz, JL. Samuel, JJ. Mercadier, D. de la Bastie, AM. Lompr4, B. Swynghedauw and L. Rappaport. U 127 INSERM, Paris, France. The ability of the myocardium to respond to physiological and pathological demands depends to an unknown extent on the plasticity of expression of contractile proteins multigene families and on the cytoskeleton organization. We have studied the species and tissue specificities and the time-course of several phenotypic changes. Transitions between a and ~ myosin heavy chains (MHC) seem to be regulated by the same stimuli in atria and ventricles although the extent of regulation is quite different for the two tissues, depending both on the initial phenotype and on the stimulus : severe hypothyroidism in rat affects mardkedly the ventricles and only slightly the atria. In contrast, chronic mechanical overloads are characterized both in rat ventricles and in human atria by significant shifts to ~ M H C (up to 80 % of total myosin). Ventricular isoactins and cytoskeletal organization (microtubules, desmin) also vary in rats in systolic overloads, but in contrast to the isomyosin changes, the responses are transitory. These results demonstrate that i) the pattern of expression of the different cardiac genes are not regulated in a coordinate fashion and ii) the myocardium responds to mechanical stimuli by two mechanisms, one transitory perhaps related to cardiac growth, and one non-transitory perhaps related to the production of new proteins best suited for the new environmental situation.
99CARDIAC MYOSINS: DISTRIBUTION OF MYOSIN HEAVY CHAIN ISOFORMS IN ORDINARY MYOCARDIUM AND CONDUCTION TISSUE. S. Schiaffino, L. Gorza, S. Sartore, L. Saggin. I n s t i t u t e of General Pathology, University of Padova, Padova, I t a l y . Polyclonal and monoclonal antibodies reacting s p e c i f i c a l l y with sarcomeric myosin heavy chains (MHCs) have been used to study the d i s t r i b u t i o n of d i f f e r e n t myosin isoforms in the mammalian heart. Three main types of MHCs have been identified: I) ~-MHC, the predominant form in the a t r i a l myocardium, 2) ~-MHC, which in large mammals is the major form in the v e n t r i c u l a r myocardium, and 3) nodal-MHC, a d i s t i n c t isoform s p e c i f i c a l l y localized in muscle c e l l s of the s i n o - a t r i a l and a t r i o - v e n t r i c u l a r nodes. In the bovine heart nodal-MHC appears to be a n t i g e n i c a l l y s i m i l a r but not i d e n t i c a l to MHCs present in f e t a l skeletal muscle. Immunoflurescence and immunoperoxidase studies show marked c e l l u l a r heterogeneity in myosin composition of nodal and perinodal tissue and internodal t r a c t s . The functional significance of regional variations in the d i s t r i b u t i o n of MHC isoforms in the mammalian heart w i l l be discussed.