- Email: [email protected]
Crossbridge dynamics in rat papillary muscles containing V1 and V3 isomyosins: Effect of adrenaline
MYOSIN LIGHT CHAIN ISOENZYME TRANSITIONS IN THE DEVELOPING AND ADULT HUMAN HEART. P. Cummins. Molecular Cardiology Unit, Department of Cardiovascular Medicine, University of Birmingham, Birmingham, B15 2TH, U.K. To establish the role of myosin isoenayme transitions in the pathogenesis of cardiac overload, it is essential to determine the normal pattern of isoenzyme expression. Light chain isoenzymes of myosin have been studied in the human atrium and ventricle from mid-foetal gestation to late adult life using analytical electrophoretic techniques. The results obtained have been compared to the known changes in pressure gradients in each cardiac chamber. During foetal and early neonatal development both ventricular and atrial-type light chain isoenzymes are present in right and left ventricle. The atria1 isoensyme makes up 50% of the total population at midgestation but disappears during the first 1 to 2 years postnatally to be replaced by the ventricular form. During the same period, only atria1 light chains can be detected in the atria. Although no evidence is obtained for transitions in the adult ventricle, marked changes occur in the atria1 chambers which resemble the transitions in the developing ventricle. Both transitions appear to involve atria1 to ventricular switches and may proceed preferentially via different light chain types. The light chain populations have been investigated during cardiac pressure and volume overload in a large number of adult patients undergoing cardiac surgery and in children with both congenital and compensatory hypertrophic heart disease.
CROSSBRIDGE DYNAMICS IN RAT PAPILLARY MUSCLES CONTAINING V1 AND V3 ISOMYOSINS: EFFECT OF ADRENALINE. J.F.Y. Hoh* and G.H. Rossmanith, Department of Physiology*, University of Sydney, N.S.W., 2006, and School of Mathematcis and Physics, Macquarie University, North Ryde, N.S.W. 2113, Australia. We show, by means of perturbation analysis, that the rate of crossbridge cycling of Vl and V3 containing papillary muscles at 25’C is (mean * S.D.) 2.1 f 0.2 tlz (n=lO) and 1.1 l 0.2 Hz (n=8) respectively. Muscles in barium contracture were analysed in this way to determine whether the inotropic action of adrenaline is associated with an increased rate of crossbridge cycling. The results showed that adrenaline increased the rate in V, hearts by 50 f 6% (n=6). The action on V3 hearts was significantly less at the same dose (1 rig/ml), the increase in rate being 25 * 4% (n=6). The increase in crossbridge cycling rate for Vl hearts was shown to be sensitive to the 6 blocking agent propranolol (3 Rg/ml). These results suggest that adrenaline significantly alters the rate of crossbridge cycling by a receptor mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins, but also from the increased rate at which each crossbridge can transduce energy.
A COMPARISON OF CONTRACTILE AND REGULATORY PROTEIN EXPRESSION IN THE MYOCARDIUM OF SMALL AND LARGE MAMMALS; IMPLICATIONS FOR STUDIES ON CARDIAC OVERLOAD. P. Cummins, J.E. Humphreys, S.J. Lambert and R.A. Janes. Mol,ecular Cardiology Unit, Department of Cardiovascular Medicine, University of Bir~ngh~,,::Bf~~ngham, B15 2TH, U.K. Cardiac adaption to changing.pr~~~~~re'alid: volume'loads -may depend on the expression of different isoforms of contrectiie'and regulatory proteins. Eviden&e that these mechanisms are employed in the &ntricles, of .smaLl mainmals, e..g..rat $id rabbit, is widespread and based On existence of heavy chain isafo'smp of myos,in:tith different primary sequences and ATPase,'actiVities. We have carried out a auhei of the contractile and regulatory protein isoforms present in larger &ssaalian hear'&. Troponin-I, the inhibitory protein of the regulatory complex, shows no evidence of,.&$$ferent isoforms in rhesus monkey, baboon or human, atria1 and ventricular myocaihiu&~ This apparent invariance exists at all developmental stages and in.thb adult.'Po$&intial for changes in post-translational modifications such as phosphoiqrlation m‘ay however exist. Tropomyosin was present in ca and S isoforms, in atria and'ventrioles at most developmental stages. Although different types of a and S isoforms-+sre not detected, the relative proportions changed developmentally and also correlated &ith heart rate in different species. Changes in phosphorylation were also apparent. Only one myosin heavy chain isoform was apparent in the ventricle although two were present in the atria. Light chain myosin isoenzvmes were nresent in several different forms and
CROSSBRIDGE DYNAMICS IN RAT PAPILLARY MUSCLES CONTAINING V1 AND V3 ISOMYOSINS: EFFECT OF ADRENALINE. J.F.Y. Hoh* and G.H. Rossmanith, Department of Physiology*, University of Sydney, N.S.W., 2006, and School of Mathematcis and Physics, Macquarie University, North Ryde, N.S.W. 2113, Australia. We show, by means of perturbation analysis, that the rate of crossbridge cycling of Vl and V3 containing papillary muscles at 25’C is (mean * S.D.) 2.1 f 0.2 tlz (n=lO) and 1.1 l 0.2 Hz (n=8) respectively. Muscles in barium contracture were analysed in this way to determine whether the inotropic action of adrenaline is associated with an increased rate of crossbridge cycling. The results showed that adrenaline increased the rate in V, hearts by 50 f 6% (n=6). The action on V3 hearts was significantly less at the same dose (1 rig/ml), the increase in rate being 25 * 4% (n=6). The increase in crossbridge cycling rate for Vl hearts was shown to be sensitive to the 6 blocking agent propranolol (3 Rg/ml). These results suggest that adrenaline significantly alters the rate of crossbridge cycling by a receptor mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins, but also from the increased rate at which each crossbridge can transduce energy.
A COMPARISON OF CONTRACTILE AND REGULATORY PROTEIN EXPRESSION IN THE MYOCARDIUM OF SMALL AND LARGE MAMMALS; IMPLICATIONS FOR STUDIES ON CARDIAC OVERLOAD. P. Cummins, J.E. Humphreys, S.J. Lambert and R.A. Janes. Mol,ecular Cardiology Unit, Department of Cardiovascular Medicine, University of Bir~ngh~,,::Bf~~ngham, B15 2TH, U.K. Cardiac adaption to changing.pr~~~~~re'alid: volume'loads -may depend on the expression of different isoforms of contrectiie'and regulatory proteins. Eviden&e that these mechanisms are employed in the &ntricles, of .smaLl mainmals, e..g..rat $id rabbit, is widespread and based On existence of heavy chain isafo'smp of myos,in:tith different primary sequences and ATPase,'actiVities. We have carried out a auhei of the contractile and regulatory protein isoforms present in larger &ssaalian hear'&. Troponin-I, the inhibitory protein of the regulatory complex, shows no evidence of,.&$$ferent isoforms in rhesus monkey, baboon or human, atria1 and ventricular myocaihiu&~ This apparent invariance exists at all developmental stages and in.thb adult.'Po$&intial for changes in post-translational modifications such as phosphoiqrlation m‘ay however exist. Tropomyosin was present in ca and S isoforms, in atria and'ventrioles at most developmental stages. Although different types of a and S isoforms-+sre not detected, the relative proportions changed developmentally and also correlated &ith heart rate in different species. Changes in phosphorylation were also apparent. Only one myosin heavy chain isoform was apparent in the ventricle although two were present in the atria. Light chain myosin isoenzvmes were nresent in several different forms and