The mechano‐kinetic properties of the cardiac myosin were studied in situ, in trabeculae dissected from the right ventricle of the rat heart, by measuring the stiffness of the half‐sarcomere both at the twitch force peak (Tp) of an electrically paced intact trabecula at different extracellular Ca2+ concentrations ([Ca2+]o), and in the same trabecula after skinning and induction of rigor. Taking into account the contribution of filament compliance to half‐sarcomere compliance and the lattice geometry, we found that the stiffness of the cardiac myosin motor is 1.07 ± 0.09 pN nm–1, which is slightly larger than that of the slow myosin isoform of skeletal muscle (0.6‐0.8 pN nm–1) and 2‐ to 3‐fold smaller than that of the fast skeletal muscle isoform. The increase in Tp from 61 ± 4 kPa to 93 ± 9 kPa, induced by raising [Ca2+]o from 1 to 2.5 mm at sarcomere length ∼2.2 μm, is accompanied by an increase of the half‐sarcomere stiffness that is explained by an increase of the fraction of actin‐attached motors from 0.08 ± 0.01 to 0.12 ± 0.02, proportional to Tp. Consequently, each myosin motor bears an average force of 6.14 ± 0.52 pN independently of Tp and [Ca2+]o. The application of fast sarcomere‐level mechanics to intact trabeculae to define the mechano‐kinetic properties of the cardiac myosin in situ represents a powerful tool for investigating cardiomyopathy‐causing mutations in the myosin motor and testing specific therapeutic interventions.

The force and stiffness of myosin motors in the isometric twitch of a cardiac trabecula and the effect of the extracellular calcium concentration / Pinzauti, Francesca; Pertici, Irene; Reconditi, Massimo; Narayanan, Theyencheri; Stienen, Ger J. M.; Piazzesi, Gabriella; Lombardi, Vincenzo; Linari, Marco; Caremani, Marco*. - In: THE JOURNAL OF PHYSIOLOGY. - ISSN 0022-3751. - STAMPA. - 596:(2018), pp. 2581-2596. [10.1113/JP275579]

The force and stiffness of myosin motors in the isometric twitch of a cardiac trabecula and the effect of the extracellular calcium concentration

PINZAUTI, FRANCESCA;PERTICI, IRENE;Reconditi, Massimo;Piazzesi, Gabriella;Lombardi, Vincenzo;Linari, Marco
;
Caremani, Marco
2018

Abstract

The mechano‐kinetic properties of the cardiac myosin were studied in situ, in trabeculae dissected from the right ventricle of the rat heart, by measuring the stiffness of the half‐sarcomere both at the twitch force peak (Tp) of an electrically paced intact trabecula at different extracellular Ca2+ concentrations ([Ca2+]o), and in the same trabecula after skinning and induction of rigor. Taking into account the contribution of filament compliance to half‐sarcomere compliance and the lattice geometry, we found that the stiffness of the cardiac myosin motor is 1.07 ± 0.09 pN nm–1, which is slightly larger than that of the slow myosin isoform of skeletal muscle (0.6‐0.8 pN nm–1) and 2‐ to 3‐fold smaller than that of the fast skeletal muscle isoform. The increase in Tp from 61 ± 4 kPa to 93 ± 9 kPa, induced by raising [Ca2+]o from 1 to 2.5 mm at sarcomere length ∼2.2 μm, is accompanied by an increase of the half‐sarcomere stiffness that is explained by an increase of the fraction of actin‐attached motors from 0.08 ± 0.01 to 0.12 ± 0.02, proportional to Tp. Consequently, each myosin motor bears an average force of 6.14 ± 0.52 pN independently of Tp and [Ca2+]o. The application of fast sarcomere‐level mechanics to intact trabeculae to define the mechano‐kinetic properties of the cardiac myosin in situ represents a powerful tool for investigating cardiomyopathy‐causing mutations in the myosin motor and testing specific therapeutic interventions.
2018
596
2581
2596
Goal 3: Good health and well-being for people
Pinzauti, Francesca; Pertici, Irene; Reconditi, Massimo; Narayanan, Theyencheri; Stienen, Ger J. M.; Piazzesi, Gabriella; Lombardi, Vincenzo; Linari, Marco; Caremani, Marco*
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1131031
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