Strongly binding myosin crossbridges regulate loaded shortening and power output in cardiac myocytes.

Abstract:

:This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during varying levels of Ca(2+) activation. Lowering the [Ca(2+)] slowed shortening velocities, decreased relative power output, and increased the curvature of length traces. We tested the hypothesis that Ca(2+) activation dependence of loaded shortening is determined primarily by strongly binding crossbridges or by [Ca(2+)] per se, which was done by measuring loaded shortening before and after addition of N-ethylmaleimide-conjugated myosin subfragment-1 (NEM-S1), a strongly binding myosin analogue that cooperatively enhances thin filament activation. At fixed [Ca(2+)], NEM-S1 reduced the curvature of length traces and sped loaded shortening velocities. Even when [Ca(2+)] was adjusted so that force was equal with and without NEM-S1, myocyte shortening was faster and exhibited less curvature with NEM-S1. In the presence of NEM-S1, peak relative power output was also significantly greater during activations either at the same [Ca(2+)] or when [Ca(2+)] was adjusted to achieve the same force. Consequently, NEM-S1 eliminated any Ca(2+) dependence of relative power output that is normally observed in cardiac myocytes. These results indicate that strongly binding crossbridges play a significant role in determining loaded shortening and power output and suggest that previously observed Ca(2+) dependence of power output is mediated by alterations in numbers of crossbridges bound to the thin filament.

journal_name

Circ Res

journal_title

Circulation research

authors

McDonald KS,Moss RL

doi

10.1161/01.res.87.9.768

subject

Has Abstract

pub_date

2000-10-27 00:00:00

pages

768-73

issue

9

eissn

0009-7330

issn

1524-4571

journal_volume

87

pub_type

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