Myosin MgADP release rate decreases at longer sarcomere length to prolong myosin attachment time in skinned rat myocardium.

08:00 EDT 16th October 2015 | BioPortfolio

Summary of "Myosin MgADP release rate decreases at longer sarcomere length to prolong myosin attachment time in skinned rat myocardium."

Cardiac contractility increases as sarcomere length increases, suggesting that intrinsic molecular mechanisms underlie the Frank-Starling relationship to confer increased cardiac output with greater ventricular filling. Myosin's capacity to bind with actin and generate force in a muscle cell is Ca(2+)-regulated by thin-filament proteins and spatially-regulated by sarcomere length as thick-to-thin filament overlap varies. One mechanism underlying greater cardiac contractility as sarcomere length increases could involve longer myosin attachment time (ton) due to slowed myosin kinetics at longer sarcomere length. To test this idea, we used stochastic length-perturbation analysis in skinned rat papillary muscle strips to measure ton as [MgATP] varied (0.05-5 mM) at 1.9 and 2.2 µm sarcomere lengths. From this ton-MgATP relationship, we calculated cross-bridge MgADP release rate and MgATP binding rates. As MgATP increased, t_on decreased for both sarcomere lengths, but ton was roughly 70% longer for 2.2 vs. 1.9 µm sarcomere length at maximally-activated conditions. These ton differences were driven by a slower MgADP release rate at 2.2 µm sarcomere length (41±3 vs. 74±7 s(-1)), as MgATP binding rate was not different between the two sarcomere lengths. At sub-maximal activation levels near the pCa50 value of the tension-pCa relationship for each sarcomere length, length-dependent increases in ton were roughly 15% longer for 2.2 vs. 1.9 µm sarcomere length. These changes in cross-bridge kinetics could amplify cooperative cross-bridge contributions to force production and thin-filament activation at longer sarcomere length, and suggest that length-dependent changes in myosin MgADP release rate may contribute to the Frank-Starling relationship in the heart.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539
Pages: ajpheart.00555.2015


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Medical and Biotech [MESH] Definitions

A subclass of myosin found in ACANTHAMOEBA. It is a non-filamentous myosin containing a single 180-kDa myosin heavy chain.

Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).

The subfamily of myosin proteins that are commonly found in muscle fibers. Myosin II is also involved a diverse array of cellular functions including cell division, transport within the GOLGI APPARATUS, and maintaining MICROVILLI structure.

A subclass of myosin involved in organelle transport and membrane targeting. It is abundantly found in nervous tissue and neurosecretory cells. The heavy chains of myosin V contain unusually long neck domains that are believed to aid in translocating molecules over large distances.

An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.

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