Alpha and beta myosin isoforms and human atrial and ventricular contraction

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03971-y ◽

2021 ◽

Author(s):

Jonathan Walklate ◽

Cecilia Ferrantini ◽

Chloe A. Johnson ◽

Chiara Tesi ◽

Corrado Poggesi ◽

...

Keyword(s):

Mechanical Characteristics ◽

Essential Feature ◽

Myosin Isoforms ◽

Cardiac Myosin ◽

Ventricular Contraction ◽

Functional Characteristics

AbstractHuman atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles.

Download Full-text

Myosins and pathology: genetics and biology.

Acta Biochimica Polonica ◽

10.18388/abp.2002_3739 ◽

2002 ◽

Vol 49 (4) ◽

pp. 789-804 ◽

Cited By ~ 34

Author(s):

Maria Jolanta Redowicz

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Myosin Heavy Chain ◽

Inner Ear ◽

Heavy Chain ◽

Hair Cells ◽

Familial Hypertrophic Cardiomyopathy ◽

Light Chains ◽

Myosin Isoforms ◽

Cardiac Myosin ◽

Genes Encoding

This article summarizes current knowledge on the genetics and possible molecular mechanisms of Human pathologies resulted from mutations within the genes encoding several myosin isoforms. Mutations within the genes encoding some myosin isoforms have been found to be responsible for blindness (myosins III and VIIA), deafness (myosins I, IIA, IIIA, VI, VIIA and XV) and familial hypertrophic cardiomyopathy (beta cardiac myosin heavy chain and both the regulatory and essential light chains). Myosin III localizes predominantly to photoreceptor cells and is proved to be engaged in the vision process in Drosophila. In the inner ear, myosin I is postulated to play a role as an adaptive motor in the tip links of stereocilia of hair cells, myosin IIA seems to be responsible for stabilizing the contacts between adjacent inner ear hair cells, myosin VI plays a role as an intracellular motor transporting membrane structures within the hair cells while myosin VIIA most probably participates in forming links between neighbouring stereocilia and myosin XV probably stabilizes the stereocilia structure. About 30% of patients with familial hypertrophic cardiomyopathy have mutations within the genes encoding the beta cardiac myosin heavy chain and both light chains that are grouped within the regions of myosin head crucial for its functions. The alterations lead to the destabilization of sarcomeres and to a decrease of the myosin ATPase activity and its ability to move actin filaments.

Download Full-text

Inhibition by theophylline of the early component of canine ventricular contraction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.242.3.h349 ◽

1982 ◽

Vol 242 (3) ◽

pp. H349-H358

Author(s):

M. Endoh ◽

T. Iijima ◽

S. Motomura

Keyword(s):

Mechanical Characteristics ◽

Calcium Influx ◽

Myocardial Cell ◽

Ventricular Muscle ◽

Late Component ◽

Ventricular Contraction ◽

Early Component ◽

Peak Tension ◽

Time To Peak ◽

Plateau Potential

Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37 degrees C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol increased preferentially the early component and affected only slightly the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component, whereas the increase in the early one induced by isoproterenol in 3 X 10(-7) M and higher was depressed significantly. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the calcium influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. These results indicate that theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.

Download Full-text

Cardiac Myosin Binding Protein-C Influences the Rates of MgADP Release and MgATP Binding Differently for the Two Cardiac Myosin Isoforms Expressed in Mouse Myocardium

Biophysical Journal ◽

10.1016/j.bpj.2012.11.1052 ◽

2013 ◽

Vol 104 (2) ◽

pp. 186a

Author(s):

Bertrand C. Tanner ◽

Yuan Wang ◽

Jeffrey Robbins ◽

Brad Palmer

Keyword(s):

Protein C ◽

Binding Protein ◽

Myosin Isoforms ◽

Cardiac Myosin ◽

Myosin Binding Protein ◽

Myosin Binding Protein C ◽

Myosin Binding

Download Full-text

Kinetics of cardiac myosin isoforms in mouse myocardium are affected differently by presence of myosin binding protein-C

Journal of Muscle Research and Cell Motility ◽

10.1007/s10974-014-9390-0 ◽

2014 ◽

Vol 35 (5-6) ◽

pp. 267-278 ◽

Cited By ~ 11

Author(s):

Bertrand C. W. Tanner ◽

Yuan Wang ◽

Jeffrey Robbins ◽

Bradley M. Palmer

Keyword(s):

Protein C ◽

Binding Protein ◽

Myosin Isoforms ◽

Cardiac Myosin ◽

Myosin Binding Protein ◽

Myosin Binding Protein C ◽

Myosin Binding ◽

Kinetics Of

Download Full-text

Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms

The Journal of Physiology ◽

10.1111/j.1469-7793.1999.0669n.x ◽

1999 ◽

Vol 519 (3) ◽

pp. 669-678 ◽

Cited By ~ 88

Author(s):

Kimberly A. Palmiter ◽

Matthew J. Tyska ◽

Donald E. Dupuis ◽

Norman R. Alpert ◽

David M. Warshaw

Keyword(s):

Functional Diversity ◽

Single Molecule ◽

Myosin Isoforms ◽

Cardiac Myosin ◽

Single Molecule Level

Download Full-text

Molecular mechanics of mouse cardiac myosin isoforms

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00274.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. H1446-H1454 ◽

Cited By ~ 58

Author(s):

Norman R. Alpert ◽

Christine Brosseau ◽

Andrea Federico ◽

Maike Krenz ◽

Jeffrey Robbins ◽

...

Keyword(s):

Molecular Structure ◽

Amino Acids ◽

Mechanical Performance ◽

Structure And Function ◽

Myosin Isoforms ◽

Myofibrillar Atpase ◽

Cardiac Myosin ◽

Average Force ◽

And Function ◽

Molecular Structure And Function

Two myosin isoforms are expressed in myocardium, αα-homodimers (V1) and ββ-homodimers (V3). V1exhibits higher velocities and myofibrillar ATPase activities compared with V3. We also observed this for cardiac myosin from normal (V1) and propylthiouracil-treated (V3) mice. Actin velocity in a motility assay ( V actin) over V1 myosin was twice that of V3 as was the myofibrillar ATPase. Myosin's average force (Favg) was similar for V1 and V3. Comparing V actin and Favg across species for both V1 and V3, our laboratory showed previously (VanBuren P, Harris DE, Alpert NR, and Warshaw DM. Circ Res 77: 439–444, 1995) that mouse V1 has greater V actin and Favg compared with rabbit V1. Mouse V3 V actin was twice that of rabbit V actin. To understand myosin's molecular structure and function, we compared α- and β-cardiac myosin sequences from rodents and rabbits. The rabbit α- and β-cardiac myosin differed by eight and four amino acids, respectively, compared with rodents. These residues are localized to both the motor domain and the rod. These differences in sequence and mechanical performance may be an evolutionary attempt to match a myosin's mechanical behavior to the heart's power requirements.

Download Full-text