Stehle, Robert (2017). Force Responses and Sarcomere Dynamics of Cardiac Myofibrils Induced by Rapid Changes in [P-i]. Biophys. J., 112 (2). S. 356 - 368. CAMBRIDGE: CELL PRESS. ISSN 1542-0086

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Abstract

The second phase of the biphasic force decay upon release of phosphate from caged phosphate was previously interpreted as a signature of kinetics of the force-generating step in the cross-bridge cycle. To test this hypothesis without using caged compounds, force responses and individual sarcomere dynamics upon rapid increases or decreases in concentration of inorganic phosphate [P-i] were investigated in calcium-activated cardiac myofibrils. Rapid increases in [P-i] induced a biphasic force decay with an initial slow decline (phase 1) and a subsequent 3-5-fold faster major decay (phase 2). Phase 2 started with the distinct elongation of a single sarcomere, the so-called sarcomere give. Give then propagated from sarcomere to sarcomere along the myofibril. Propagation speed and rate constant of phase 2 (k(+Pi(2))) had a similar [P-i]-dependence, indicating that the kinetics of the major force decay (phase 2) upon rapid increase in [P-i] is determined by sarcomere dynamics. In contrast, no give was observed during phase 1 after rapid [P-i]-increase (rate constant k(+Pi(1))) and during the single-exponential force rise (rate constant k(-pi)) after rapid [Pa-decrease. The values of k(+pi(1)) and k(-pi) were similar to the rate constant of mechanically induced force redevelopment (k(TR)) and Ca2+-induced force development (kACT) measured at same [P-i]. These results indicate that the major phase 2 of force decay upon a P-i-jump does not reflect kinetics of the force-generating step but results from sarcomere give. The other phases of P-i-induced force kinetics that occur in the absence of give yield the same information as mechanically and Ca2+-induced force kinetics (k(+Pi(1)) similar to k(-Pi) similar to k(TR) similar to k(ACT)). Model simulations indicate that P-i-induced force kinetics neither enable the separation of P-i-release from the rate-limiting transition f into force states nor differentiate whether the force generating step occurs before, along, or after the P-i-release.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Stehle, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-242266
DOI: 10.1016/j.bpj.2016.11.005
Journal or Publication Title: Biophys. J.
Volume: 112
Number: 2
Page Range: S. 356 - 368
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1542-0086
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RABBIT PSOAS MUSCLE; CROSS-BRIDGE ACTION; PHOSPHATE RELEASE; SKELETAL-MUSCLE; STRIATED-MUSCLE; TENSION RECOVERY; WORKING STROKE; SKINNED FIBERS; GENERATION; MYOSINMultiple languages
BiophysicsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24226

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